Genome-wide association analysis of the primary feather growth traits of duck: identification of potential Loci for growth regulation.
The feather is an important epidermal appendage, plays an important role in the life activities of avian specie, and has important economic value. Revealing the molecular regulation mechanism of feather growth has a significant meaning in studying adaptive evolution, physiology, and mating of avian species and also provides a theoretical reference for poultry breeding. In this study, the genome-wide association analysis (GWAS) of 358 ducks was based on primary feather length phenotypic data (28-60 d), length growth rates (LGRs), and maturity scores (60 d) to explore the genetic basis affecting feather growth and maturation. The results showed that, among the primary feather 1 to 5 in ducks, the mean LGR of primary feather 2 was the fastest, with the longest length. The primary feathers in males grew and matured slightly faster than in females. The mean maturity scores of primary feather 10∼7 were higher than primary feather 1 to 3 in ducks. GWAS further showed 116 SNPs associated with feather length traits. In addition, 2 candidate regions (Chr1: 127,407,230-127,524,879 bp and Chr21: 182,061,707-183,616,298 bp) were associated with LGR, which contain total 13 candidate genes (The extremely significant SNPs were mainly located in 2 genes: Chr1: REPS2 and Chr21: PTPRT). Four candidate regions (Chr1: 29,113,036-28,675,018 bp, Chr2: 18,253,612-149,111,290 bp, Chr15: 6,489,774 to 12,138,221 bp and Chr21: 6,578,021-8,472,904 bp) were associated with feather maturity, which contain total 24 candidate genes (The extremely significant SNPs were mainly located in 4 genes: Chr1: IMMP2L, DOCK4 and DDX10, Chr2: LDLRAD4). In conclusion, sex factors influence feather growth and maturity, and the genetic basis of the growth /maturity trait between different feathers is similar. REPS2, PTPRT genes, and IMMP2L, DOCK4, DDX10, and LDLRAD4 are important candidate genes that influence feather growth and maturity, respectively.


Adenosine triphosphate (ATP) treatment of hypoxic pulmonary hypertension (HPH): comparison of dose dependence in pulmonary and renal circulations.
In this study we investigated the relationship between pulmonary and renal responses to a low dose infusion of adenosine triphosphate-magnesium chloride (ATP-MgCl2) in a newborn piglet model of hypoxic pulmonary hypertension (HPH). Three- to five-day-old piglets were cannulated for the measurement of pulmonary and systemic arterial pressure, pulmonary and renal artery flow, and urine output. The animals were then made hypoxic by ventilation with a mixture containing 10% oxygen, 4% CO2, and balance nitrogen. Serial infusions of ATP-MgCl2 at 0.01, 0.025, 0.05, 0.1, 0.5, and 1.0 mg/kg/min were compared to preinfusion hypoxia baselines. Hypoxia alone produced a significant elevation in pulmonary artery pressure (73%) and a reduction in pO2. All dose rates of ATP-MgCl2 greater than or equal to 0.05 mg/kg/min produced a significant decrease in mean pulmonary artery pressure. However, as baseline mean pulmonary artery pressure increased there was an increased sensitivity to ATP-induced vasodilation. Pulmonary artery flow did not change during ATP infusion, thus, the change in pulmonary vascular resistance accounted for the decrease in pulmonary artery pressure. In contrast to the response of the pulmonary vasculature, systemic pressure was significantly decreased only during the 1.0 mg/kg/min infusion. Renal blood flow decreased by 46% during hypoxia and decreased further only during the highest dose rate of ATP infused (i.e., 1.0 mg/kg/min). Creatinine clearance (Ccr) and fractional reabsorption of Na (FreNa) also fell during hypoxia, but were not further altered during all but the highest dose of ATP infused.(ABSTRACT TRUNCATED AT 250 WORDS)


Laparoscopic inguinal hernia repair: transabdominal preperitoneal (TAPP) versus totally extraperitoneal (TEP) approach: a prospective randomized controlled trial.
Minimal access approaches to inguinal hernia repair have added to the ongoing debate over the "best groin hernia repair." The present prospective randomized controlled trial was done to compare the totally extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) techniques of laparoscopic inguinal hernia repair. The present prospective randomized study was conducted between May 2007 and March, 2009 and included 100 patients suffering from uncomplicated primary groin hernia. Patients were randomized into group I (TEP) and group II (TAPP). Intraoperative variables and postoperative pain scores were recorded in a prestructured form. One hundred patients were included in the study (TEP, 53; TAPP, 47). Both groups were comparable in terms of demographic profile and hernia characteristics. The average operative time was higher in the TAPP group (p = 0.209). The pain scores at 1 h and 24 h after surgery and at 3-month follow-up were significantly higher in the TAPP group (p < 0.05). The average follow-up was 30.5 months. In the TEP group, 37.8% of patients had seroma compared to 18.3% in the TAPP group (p = 0.021). However, there was a higher incidence of scrotal edema in the TAPP group (16 vs. 9, p = 0.009). The wound infection rates were equal (2% vs. 3%). There has been no recurrence in either group during the follow-up period of 44 months. Overall, the patients were more satisfied with TEP rather than TAPP (p < 0.05). In the present study, TEP had a significant advantage over TAPP for significantly reduced postoperative pain up to 3 months, which resulted in a better patient satisfaction score. The other intraoperative complications, postoperative complications, and cost were similar in both groups. In terms of results, both repair techniques seemed equally effective, but TEP had an edge over TAPP.


Bio-robotic cues show how the Trinidadian guppy male recognises the morphological features of receptive females.
Sensory fusion is used by the males of several animal species to discriminate the mating status of females by evaluating their phenotypic traits. The predominant trait used is olfactory cues, and the role of visual cues is not yet fully understood. The ability of Poecilia reticulata males to evaluate females' receptivity based on visual cues was investigated. Guppy males adopt two different mating strategies, courtship displays and forced copulation, towards receptive and pregnant females, respectively. Robotic counterparts mimicking receptive and pregnant females were developed to test whether males relied only on visual information to determine a females' mating status. Exposure to the robotic receptive females evoked courtship behaviours, while forced copulation attempts were more frequent towards the robotic pregnant females. When the robotic fish were simultaneously exposed, regardless of the presence or absence of receptive-female olfactory cues, males expressed their preference for the receptive female. Visual processing showed that fish social interactions played a strategic role in their collection of information, especially when other stimuli were not available. The proposed ethorobotic approach allowed for assessing the role of visual cues in the mating choice of P. reticulata males and highlighting the information processing methods and cognition in aquatic animals.


Ideomotor apraxia and aphasia: an examination of types and manifestations of apraxic symptoms.
Eighty-eight aphasic patients with the four standard syndromes as well as two control groups, 10 right-sided brain damaged patients and 10 patients without brain damage were examined for ideomotor apraxia by means of 200 tasks. The tasks required oral, arm, leg and bimanual movements, both on verbal command and on imitation. The limb movements were half meaningful, half meaningless. Performances were evaluated according to five response categories: correct, fragmentary, augmentative, perseveratory, other errors. The aim of the investigation was to ascertain whether there are apractic syndromes which are either related to the aphasic syndromes or are characterized by certain types of errors or by manifestation on certain parts of the body. The findings were negative in all three respects. The meaning of these findings for the organization of praxis and language is discussed. The performances of the control groups were consistently higher than those of the aphasic patients.


Physical outcome and quality of life after total esophagogastric dissociation in children with severe neurodisability and gastroesophageal reflux, from the caregiver's perspective.
The objective of this study is to retrospectively assess the surgical outcome and the quality of life (QOL) from the caregiver's perspective after total esophagogastric dissociation in neurologically impaired (NI) children with gastroesophageal reflux (GOR). Based on O'Neill questionnaire, a QOL questionnaire was designed, which was completed by the caregivers recording the child's well being and caregiver's satisfaction preprocedure, immediately (6 months), and long-term postprocedure (median, 21 months; range, 4-38). Statistical analysis was done using Kruskal-Wallis Test and Dunn's multiple comparisons test. Twenty-three children underwent surgery between 2003 and 2008; 19 families participated. Ease of feeding improved significantly both immediately and long term. Statistically significant improvements were also seen in comfort and ability of the child to enjoy life, frequency of medical visits, vomiting, retching, and choking. Postoperatively, caring for the child became easier, and the caregiver's frustration in caring improved statistically, but the caregiver's overall QOL did not improve significantly. Total esophagogastric dissociation has huge positive impact on the physical well being of the NI children experiencing GOR. The overall view of the procedure is one of success surpassing all expectations. Therefore, it should be considered alongside other antireflux procedures in NI children.


Enhancement by stable butyrate derivatives of antitumor and antiviral actions of interferon.
The use of n-butyric acid has been associated with induction of cell differentiation and bypassing of genetic defects in the suppression of malignancy. This biological response modifier satisfies the requirements for specificity and low toxicity, and its use can be considered as an alternative approach to conventional cancer chemotherapy. However, a lack of clinical efficacy has been observed with butyrate and attributed mainly to the rapid metabolism of the compound. Butyric acid pro-drugs derived from monosaccharides such as 3-O-butanoyl-1,2-O-isopropylidene-alpha-D-glucofuranose (MAG = 3but) have consequently been devised. Pharmacokinetic and biological advantages of MAG = 3but have been previously described. In the present report, we have studied the effect of MAG = 3but on murine interferon-alpha, beta (IFN) anticellular, antitumor and antiviral activities. In vitro, it appears that MAG = 3but predisposes malignant MSV cells to a later, complete establishment of the antiproliferative and the cell-differentiating effects of IFN, and the antiviral action of the latter in the same line of cells infected with encephalomyocarditis (EMC) virus. In vivo, combined treatment with MAG = 3but and IFN protects mice effectively against the fatal development of ascitic sarcoma 180 TG and the lethal effect of EMC virus infection.


Ultrastructural organization of giant neurones of the mollusc Lymnaea stagnalis under different environmental temperatures.
The ultrastructure of identified giant neurones of the visceral ring of Lymnaea stagnalis ganglion alters with the seasonal change of the animal and, experimentally, from the inactive physiological state (winter time or at +4 degrees C) to an active one (spring-summer time or at +18 degrees C). The ultrastructural organization of the active animal's neurones is characterized by morphological alteration pointing to an increased metabolic activity, viz., an increased number of nucleoli, an enlarged surface of nuclear membrane and an increase in the nuclear membrane pores, appearance of a zone of free ribosomes near the nuclear membrane, changing the structure of cytosomes, abundant granular endoplasmic reticulum, increase in the number of mitochondria.


Outcome of continuous cerebral and myocardial perfusion under mild hypothermia for aortic coarctation with ventricular septal defect repair.
Controversy still exists on the use of the optimal cardiopulmonary bypass (CPB) management in aortic coarctation (CoA) with ventricular septal defect (VSD) repair. We report the outcome of patients undergoing continuous cerebral and myocardial perfusion (CCMP) under mild hypothermia. This is a retrospective analysis of 60 consecutive patients undergoing anatomic reconstruction of CoA with VSD closure between 1999 and 2011. Single arterial cannula perfusion technique was used in 15 (25%) patients, and a dual arterial cannula perfusion technique was used in 45 (75%) patients. There were no hospital or late mortalities. Average CPB time was 105 ± 28 minutes, aortic clamp 27 ± 7 minutes, and descending aortic cross-clamp time 24 ± 5 minutes. Average continuous cerebral perfusion flow was 64 ± 8 mL/kg per minute. No patient needed delayed sternal closure. Average duration of ventilation was 38 ± 20 hours, ICU stay 7 ± 3 days, and hospital stay 14 ± 6 days. No patient required revision for bleeding and/or extracorporeal membrane oxygenation support. No neurologic complications were noted. A perfusion strategy using CCMP with mild hypothermia for CoA and VSD repair is feasible and safe.


Lipoproteins in experimental nephrosis: plasma levels and composition.
Experimental nephrosis was induced in rats by administration of puromycin aminonucleoside and the levels of plasma lipoproteins were examined 7 days later and compared to controls. As determined by density ultracentrifugation, VLDL, IDL, LDL, and HDL protein levels were increased by 8, 4, 5, and 5 times, respectively. These increases were accompanied by changes in lipid and apoprotein composition. The VLDL, IDL, and LDL fractions contained less triglyceride and more phospholipid and cholesterol, while HDL lipid composition was not altered. The apoprotein composition of VLDL and IDL were not measurably altered, but LDL contained less apoE. HDL had a markedly abnormal composition characterized by an almost complete absence of apoA-IV and apoE, increased apoA-1, and decreased apoC. While increased hepatic synthesis can account for much of the observed hyperlipoproteinemia in nephrosis, the changes in lipoprotein composition suggest impaired catabolism as a contributory factor.


Patterns of physical and neurologic development in preterm children.
To evaluate the influence of medical complications, gestational age, gender, ethnicity, and socioeconomic status on the changes in anthropometric measures and severity of neurologic impairment from 6 to 54 months of age in premature and term infants. This study was a prospective longitudinal study to determine predictors of patterns of growth and neurologic outcome in low-risk (n=137) and high-risk (n=96) preterm infants compared to full-term infants (n=136). Growth modeling analyses were used to evaluate factors that might influence patterns of physical growth and changes in neurologic status. Medical risk level was a predictor of height and head circumference at 30 months and neurologic outcome. Gender was a predictor of weight gain. Medical risk level and gender predicted 13.8% and 32% of the variance in head circumference and neurologic scores, respectively. Medical complications after birth and gender are stronger influences than gestational age on patterns of growth and neurologic outcome.


The use of dermal regeneration template for treatment of complex wound with bone/tendon exposed at the forearm and hand, a prospective cohort study.
The purpose of this study was to assess the efficacy and safety of Pelnac and split-thickness skin graft for management of complex wound with underlying bone/tendon exposure at forearm and hand.This is a prospective study, beginning from March 2013 up to May 2017. There were 13 patients, with age of 31.2 years. All of them underwent the staged Pelnac and split-thickness skin graft to manage the complex wound with bone/tendon. Postoperatively, scheduled follow-up was conducted.The average follow-up was 15 months. There were no infections, wound necrosis, hematoma, or seroma during the phase when Pelnac was applied. There was 100% "take" of the Pelnac in 12/13 patients. In 11 patients, there was complete skin graft "take". Patients' satisfaction for the esthetic appearance of the grafted area was 75.0 ± 8.5/100. The VSS value was 2.9 ± 2.5. Regarding the sensory recovery, the response of "normal or near normal" could be obtained in 7/13 patients, "slight loss" in 5 patients and "significant loss" in 1 case. The average DASH score was 27.2 ± 18.5, and most patients (12/13) could obtain an acceptable ability to perform the daily activities.Pelnac dermal template is a favorable alternative to flap reconstruction in the treatment of complex wound with underlying tissues exposure.


A comparison of contraceptive procurement pre- and post-benefit change.
In 2002, the Kaiser Foundation Health Plan in California changed its coverage policy to include 100% universal coverage for the most effective forms of contraception and for emergency contraceptive pills (ECPs). This study sought to evaluate whether removing the cost of contraception as a potential barrier to utilization would lead to a change in the mix of contraceptive methods prescribed and purchased by a large health plan and whether those changes could theoretically result in averting a greater number of unintended pregnancies. A retrospective observational study was conducted to describe the mix of reversible contraceptives procured before and after the benefit change at Kaiser Permanente Northern California. We then estimated couple-years of protection (CYP) to examine whether the contraceptive mix changed to more effective reversible methods. After the contraceptive benefit change, CYP increased by 28% (from 2001-2002 to 2003-2004), while the number of females aged 15-44 enrolled in this health plan fell by 1%. CYP for intrauterine contraceptives (IUCs) and injectables rose by 137% and 32%, respectively, while CYP for the pill, patch and ring rose only by 16%. The estimated average annual contraceptive failure rate among women using hormonal contraceptives and IUCs declined from 7.0% to 6.4%. Purchasing of the ECP rose by 88%. Removal of the cost of contraception may result in increased utilization of more effective methods and ECPs.


Transparent and flexible passivation of MoS2/Ag nanowire with sputtered polytetrafluoroethylene film for high performance flexible heaters.
We demonstrated highly transparent and flexible polytetrafluoroethylene (PTFE) passivation for the MoS2/Ag nanowire (Ag NW) electrodes used in thin film heaters (TFHs). The electrical, optical, and mechanical properties of PTFE coated MoS2/Ag NW electrode were compared to the bare MoS2/Ag NW electrode to demonstrate effective passivation of the sputtered PTFE films before and after the 85 °C-85% temperature-relative humidity environment test. In addition, we investigated the performances of TFHs with PTFE/MoS2/Ag NW as a function of PTFE thickness from 50 to 200 nm. The saturation temperature (87.3 °C) of TFHs with PTFE/MoS2/Ag NW electrode is higher than that (61.3 °C) of TFHs with bare MoS2/Ag NW, even after the 85 °C-85% temperature-relative humidity environment test, due to effective passivation of the PTFE layer. This indicates that transparent PTFE film prepared by sputtering process provides effective thin film passivation for the two-dimensional (2D) MoS2 and Ag NW hybrid electrode against harsh environment condition.


[Phytotoxic activity of N,N-di-sec-butylbenzamides with alkyl substituents on the aromatic nucleus].
A new series of N,N-di,sec.butylalkylbenzamides was studied and it was found that some compounds showed particularly interesting selective phytotoxicity comparable with that shown by analogous halogen derivatives.


Correction of Brachymetatarsia and Medial Angulation of the Great Toe of Apert Foot By Distraction Osteogenesis: A Review of 7 Years of Experience.
Apert foot anomalies may cause severe problems such as pain and development of callus formation related to weight redistribution, problems with footwear, and gait disturbances that may limit their daily activities. The main purpose of this study was to review our experience with distraction osteogenesis for the correction of brachymetatarsia and the great toe angulation of the patients with Apert syndrome. This study retrospectively reviewed 7 patients (14 extremities) followed up for Apert syndrome who underwent distraction for the correction of bilateral congenital brachymetatarsia and angulation of the great toe between 2004 and 2008. Correction of the metatarsal inclination angle, the medial angulation of the great toe, the percentage of lengthening, and lengthening rates of distracted bones were evaluated. Patients ranged in age from 4 to 8 years at the distraction operation, with a mean age of 5.4±1.3 years, and the average length of follow-up was 86.6±21.0 months. The length of the first metatarsal bone increased significantly from the average length of 32.6±5.7 mm to an average of 46.7±6.5 mm (P<0.001). The mean lengthening rate and lengthening percentages of distracted bones were 0.4%±0.1%/month and 30.2%±6.4%/month, respectively. Preoperative and postoperative metatarsal inclination angles were at a mean of 43.8±5.12 and 32.6±3.8, respectively, and the correction of metatarsal inclination was considered as statistically significant (P<0.001). The mean angulation of the great toe reduced significantly from 49.8±11.76 to 13.2±8.5 degrees after distraction (P<0.001). Minor complications such as pin loosening, pin-tract infection, and early union that required reoperation were observed in 5 extremities (35.7%). Anatomic features of Apert foot may lead to complaints that may limit patients' daily activities and require as much attention as associated hand and craniofacial anomalies. Distraction appears to be an effective and safe approach for the simultaneous correction of the shortness of the first ray and medial angulation of the great toe. Level IV.


[Scapular flap, an alternative to the radial forearm flap in phalloplasty: Advantages and limitations].
Antebrachial phalloplasty is considered as the standard technique in total penile reconstruction. This technique allows the creation of a phallus and a neourethra in one step at the cost of significant sequelae of the donor site. Thus, this technique has been replaced in some centers by other techniques such as the MSLD flap or the ALT flap. However, in Western populations, these techniques require the addition of a technique dedicated to the urethroplasty. The scapular flap is a technique that is not widely described in the literature and, like the antebrachial flap, allows the creation of a phallus and a urethra in one step according to the "tube within tube" technique. The aim of the study was to detail this technique, to study its vascularization and to adapt the measurements of the flap to a western population. Six cadaveric dissections were performed in the laboratory. Intravascular injection of colored latex allowed easier identification of the vessels of interest and study of the subcutaneous vascular tree. Scapular flaps of variable size were raised to adapt the size to a Western population. Six dissections were performed in Caucasian subjects. The scapular circumflex artery was constant and had a mean diameter of 3.5mm (3.3mm-3.8mm). The mean pedicle length was 7.3cm (6.8cm-8.1cm). The size of the flaps was adapted to the subcutaneous tissue and flaps of at least 14×16cm allowed the "tube within tube" technique to be performed. The scapular flap has the advantage of allowing phalloplasty with urethroplasty to be performed at the same time. The pedicle is constant and of good diameter. In addition, the sequelae of the donor site are minimal. On the other hand, the pedicle used is short and the flap cannot be surgically reinnervated. Nevertheless, the restoration of a protective sensitivity allows the implantation of a penile prosthesis.


Interaction between chicken lymphocytes and Newcastle disease virus.
Different strains of Newcastle disease virus (NDV) were added to chicken lymphocytes and JMV-1 and MSB-1 Marek's-disease-derived tumor cell lines to determine the virus-cell interaction. NDV caused fusion and lysis of the cells, and cells supported the growth and multiplication of NDV.


Proinflammatory cytokines and lipopolysaccharides up regulate MMP-3 and MMP-13 production in Asian elephant (Elephas maximus) chondrocytes: attenuation by anti-arthritic agents.
Osteoarthritis (OA), the most common form of arthritic disease, results from destruction of joint cartilage and underlying bone. It affects animals, including Asian elephants (Elephas maximus) in captivity, leading to joint pain and lameness. However, publications regarding OA pathogenesis in this animal are still limited. Therefore, this study aimed to investigate the effect of proinflammatory cytokines, including interleukin-1 beta (IL-1β), IL-17A, tumor necrosis factor-alpha (TNF-α), and oncostatin M (OSM), known mediators of OA pathogenesis, and lipopolysaccharides on the expression of cartilaginous degrading enzymes, matrix metalloproteinase (MMP)-3 and MMP-13, in elephant articular chondrocytes (ELACs) cultures. Anti-arthritic drugs and the active compounds of herbal plants were tested for their potential attenuation against overproduction of these enzymes. Among the used cytokines, OSM showed the highest activation of MMP3 and MMP13 expression, especially when combined with IL-1β. The combination of IL-1β and OSM was found to activate phosphorylation of the mitogen-activated protein kinase (MAPK) pathway in ELACs. Lipopolysaccharides or cytokine-induced expressions were suppressed by pharmacologic agents used to treat OA, including dexamethasone, indomethacin, etoricoxib, and diacerein, and by three natural compounds, sesamin, andrographolide, and vanillylacetone. Our results revealed the cellular mechanisms underlying OA in elephant chondrocytes, which is triggered by proinflammatory cytokines or lipopolysaccharides and suppressed by common pharmacological or natural medications used to treat human OA. These results provide a more basic understanding of the pathogenesis of elephant OA, which could be useful for adequate medical treatment of OA in this animal.


Field applications of agglutination and cytoadherence assays with Plasmodium falciparum from Papua New Guinea.
Plasmodium falciparum isolates obtained directly from patients in Papua New Guinea were tested in their first cycle of growth in vitro for adherence to melanoma cells and for susceptibility to agglutination by immune serum. Binding varied among isolates and, in many cases, increased with further rounds of replication under optimal culture conditions. Binding inhibition assays and agglutination assays demonstrated extreme heterogeneity of surface antigens; apparently none of the sera from adult patients recognized all of the variants presented.


Klebsiella oxytoca (EN-B2): A novel type of simultaneous nitrification and denitrification strain for excellent total nitrogen removal during multiple nitrogen pollution wastewater treatment.
The poor total nitrogen (TN) removal rate achieved using microorganisms to treat wastewater polluted with multiple types of nitrogen was improved using a novel simultaneous nitrification and denitrification strain (Klebsiella oxytoca EN-B2). Strain EN-B2 rapidly eliminated ammonium, nitrate, and nitrite, giving maximum elimination rates of 4.58, 7.46, and 7.83 mg/(L h), respectively, equivalent to TN elimination rates of 4.35, 6.92, and 7.11 mg/(L h), respectively. The simultaneous nitrification and denitrification system gave ammonium and nitrite elimination rates of 7.14 and 9.17 mg/(L h), respectively, and a TN elimination rate ≥ 9.0 mg/(L h). Nitrogen balance calculations indicated that 51.22 %, 31.62 % and 46.82 % of TN in systems containing only ammonium, nitrite, and nitrate, respectively, were lost as nitrogenous gases. The ammonia monooxygenase, hydroxylamine oxidoreductase, nitrate reductase and nitrite reductase enzyme activities were determined. The results indicated that strain EN-B2 can be used to treat wastewater polluted with multiple types of nitrogen.


An improved extraction procedure for an HPLC method for cyclosporin A in whole blood and plasma.
Cyclosporin A (CyA) was assayed by high performance liquid chromatography (HPLC) following extraction of the whole blood or plasma with diethyl ether and chromatography on a Sep-Pak Silica cartridge. Using carefully chosen volumes and ratios of ethyl acetate and hexane in the eluting sequences on the Sep-Pak, the major interferent present in normal blood and serum was eliminated.


Microwave-assisted synthesis of pinacol boronates from aryl chlorides catalyzed by a palladium/imidazolium salt system.
[reaction: see text] Aryl chlorides bearing electron-withdrawing groups react with bis(pinacol)borane 1 to give aryl boronates in good to excellent yields in the presence of a catalyst formed in situ from Pd(OAc)(2) and the imidazolium chloride 2. The reaction is greatly accelerated when carried out under microwave heating.


[Economic criteria of comparing radionuclide diagnostic instruments].
Based on a number of general postulates a mathematical equation was derived for computing the economically justified unbalance of the prices of two different instruments for the same uses depending on concrete values of their main technical parameters. The approach thus elaborated can be used for an analysis of instruments for any uses including medical ones. The criterion suggested makes it possible as well to assess, from the economic standpoint, the efficacy of the technical servicing of the equipment.


Uncomplicated outcome after anesthesia for pediatric patients with Gaucher disease.
The purpose of this retrospective review was to highlight clinical issues relating to anesthetic management in children who present with Gaucher disease-specific features that may impact on anesthetic management and surgical outcome. Previous reports have dealt primarily with neuronopathic forms where neurological dysfunction determined the mode of anesthesia. To date, no series of routine surgeries in pediatric patients with non-neuronopathic Gaucher disease has been published. All surgeries performed in children with Gaucher retrospectively analyzed. There were 31 procedures under anesthesia in 15 pediatric patients. Twenty-seven of these (87%) involved either insertion or removal of a central venous catheter. There was no correlation between disease severity and the need for blood transfusion postoperatively [required in only eight cases (25.8%), including a total hip replacement]. No difficult intubations or other airway problems were recorded. Positioning of two patients, because of gibbus and prior to hip replacement, respectively, required special attention. We record our experience in surgeries in children with mild, non-neuronopathic type I and severe neuronopathic type III Gaucher disease, who had relatively short surgeries under general anesthesia. Attention to hematological parameters in particular can minimize postoperative bleeding, the most serious complication.


Frequency and prognostic value of mutations associated with the homologous recombination DNA repair pathway in a large pan cancer cohort.
PARP inhibitors have shown remarkable efficacy in the clinical management of several BRCA-mutated tumors. This approach is based on the long-standing hypothesis that PARP inhibition will impair the repair of single stranded breaks, causing synthetic lethality in tumors with loss of high-fidelity double-strand break homologous recombination. While this is now well accepted and has been the basis of several successful clinical trials, emerging evidence strongly suggests that mutation to several additional genes involved in homologous recombination may also have predictive value for PARP inhibitors. While this notion is supported by early clinical evidence, the mutation frequencies of these and other functionally related genes are largely unknown, particularly in cancers not classically associated with homologous recombination deficiency. We therefore evaluated the mutation status of 22 genes associated with the homologous recombination DNA repair pathway or PARP inhibitor sensitivity, first in a pan-cancer cohort of 55,586 patients, followed by a more focused analysis in The Cancer Genome Atlas cohort of 12,153 patients. In both groups we observed high rates of mutations in a variety of HR-associated genes largely unexplored in the setting of PARP inhibition, many of which were associated also with poor clinical outcomes. We then extended our study to determine which mutations have a known oncogenic role, as well as similar to known oncogenic mutations that may have a similar phenotype. Finally, we explored the individual cancer histologies in which these genomic alterations are most frequent. We concluded that the rates of deleterious mutations affecting genes associated with the homologous recombination pathway may be underrepresented in a wide range of human cancers, and several of these genes warrant further and more focused investigation, particularly in the setting of PARP inhibition and HR deficiency.


Effect of cyclopiazonic acid on membrane currents in isolated inner hair cells from guinea-pig cochlea.
Cyclopiazonic acid (CPA) is a reticulum-like intracellular Ca(2+) store depletory, which raises intracellular Ca(2+) concentration. The effect of CPA on membrane currents in isolated inner hair cells (IHCs) from guinea-pig cochlea was investigated by the patch-clamp technique in the whole-cell configuration. Four out of eight IHCs showed an augmentation of the currents and the other four cells showed an inhibition of the currents by extracellular CPA application. The activation kinetics of outward currents were not changed by CPA. Three out of four IHCs obtained from the basal part of the cochlea demonstrated augmentation, whereas three out of four IHCs from the apical part demonstrated inhibition of the currents. This result suggests that Ca(2+)-activated currents were dominant in the basal IHCs of the cochlea.


A systemic perspective on children's emotional insecurity in relation to father: links to parenting, interparental conflict and children's social well-being.
Focusing on the father-child-relationship in a family systems perspective, this paper investigates longitudinal links of parenting, interparental conflict, and positive regard by both parents, to their emotional insecurity with father and mother. Furthermore, to clarify fathers' contribution to children's social development, aspects of the relationship to both parents are jointly considered. The sample was drawn from the German family panel pairfam and included 372 family triads with parents' and children's self-reports. Findings revealed consistent associations between interparental conflict and lack of positive regard and emotional insecurity, while parenting had no independent links with children's emotional insecurity or social adjustment. Controlling for the stability of child outcomes, interparental conflict predicted children's lower prosocial behavior and higher peer rejection. In addition, peer rejection was predicted by children's emotional insecurity with father. The findings are in line with the emotional security hypothesis and highlight the importance of the father-child-relationship for developing positive peer relationships.


Physiological consequences of changes in life form of the Mexican epiphyte Tillandsia deppeana (Bromeliaceae).
The heterophyllous epiphyte Tillandsia deppeana exhibits an atmospheric habit as a juvenile and a tank form as an adult. Both juveniles and adults utilize C3 photosynthesis. This is the first report of an atmospheric form of Tillandsia which does not exhibit CAM. Photosynthetic saturation occurred at approximately 10% of full sunlight in both forms, but the adults exhibited greater rates of photosynthesis at all levels of irradiance. The adults also had a higher and broader photosynthetic temperature optimum than did the juveniles. The adults transpired at greater rates than the juveniles; however, the water use efficiencies of both forms were similar and were high for C3 plants. In both forms the photosynthetic rate decreased in response to a decrease in humidity. After 8 days without water the juveniles were able to fix CO2 throughout the day. The adults, however, exhibited a net loss of CO2 on the second day without water and thereafter. These results indicate that the water-conservative atmospheric juvenile of T. deppeana is well adapted to establishment in the epiphytic habitat.


Chemical composition and medicinal significance of Fagonia cretica: a review.
Members of the family Zygophyllaceae are distributed in arid areas of the world and are traditionally used against various health insults ranging from skin lesions to lethal cancer. Fagonia cretica Linn. is a plant having novel compounds responsive in diseases that are still considered as incurable or are curable with serious side effects. Researchers, particularly of the Asian region elaborately studied the chemical composition and pharmacological activities of this plant. But further studies are still required to evaluate this plant in clinical trials in order to save humanity from synthetic chemical drugs yet disputed as 'friends or foe'.


The role of fibrinolytic agents in the management of thrombotic complications associated with vascular access devices.
VADs have made a significant contribution to improving quality of life for patients requiring long-term therapies. Clearly, this means of vascular access has offered relief from repeated venipuncture for IV access or blood sampling. Reports of the incidence of associated noninfectious complications vary between 14% and 25%. These rates are significant and warrant the development of strategies to manage such events. Fibrinolytic therapy offers a viable option for patients who have developed complications of a thrombotic nature. Although direct IV push administration may be relatively well accepted, many questions remain regarding the delivery of continuous infusions. Questions about dosing regimens, timing and number of administrations, and the ideal route of delivery all provide fertile opportunities for collaborative research.


Accelerating guideline dissemination in nursing homes during the COVID-19 pandemic: A patient-centered randomized controlled trial.
Nursing homes were ill-equipped for the pandemic; though facilities are required to have infection control staff, only 3% have taken a basic infection control course. Little is known about the implementation of effective practices outside of the acute care setting. We proposed an intervention utilizing Project ECHO, to connect Penn State University experts with nursing home staff and administrators to explore how infection control guidelines can be implemented effectively. A stratified cluster randomized design was used to assign nursing homes to either AHRQ-funded COVID-19 ECHO or AHRQ-funded COVID-19 ECHO+. 136 nursing homes participated. There were no significant differences in COVID-19 infection rate, hospitalization, deaths, or influenza, between ECHO or ECHO+. The ECHO model has significant strengths when compared to traditional training, as it allows for remote learning delivered by a multidisciplinary team of experts and utilizes case discussions that match the context of nursing homes.


Atrial fibrillation-associated minK38G/S polymorphism modulates delayed rectifier current and membrane localization.
Atrial fibrillation (AF) is a common acquired arrhythmia with multi-factorial pathogenesis. Recently, a single nucleotide polymorphism (SNP, A/G) at position 112 in the KCNE1 gene, resulting in a glycine/serine amino acid substitution at position 38 of the minK peptide, was associated with AF occurrence (AF more frequent with minK38G); however, the functional effect of this SNP is unknown. We used patch clamp recording, confocal microscopy and protein biochemistry to study the effect of this SNP on delayed-rectifier current expression and mathematical simulation to identify potential functional consequences. The density of slow delayed rectifier current (I(Ks)) resulting from co-expression with KvLQT1 was smaller with minK38G (e.g. at +10 mV: 50+/-7 pA/pF in Chinese hamster ovary (CHO) cells, 45+/-14 pA/pF for COS-7 cells) compared to minK38S (93+/-17 pA/pF, 104+/-23 pA/pF, respectively, P<0.05 for each). I(Ks) kinetics and voltage-dependence were unaffected. Currents resulting from co-expression of human ether-a-go-go-related gene (HERG) were similar for minK38G and minK38S, e.g. upon repolarization from +10 to -50 mV: tail currents 23+/-4 pA/pF versus 22+/-5 pA/pF (P=ns). KvLQT1 membrane immunofluorescence was less in CHO cells co-expressing minK38G versus minK38S, and surface expression of KvLQT1, as determined by labelling with streptavidin/biotin, was increased with minK38S co-expression. Computer simulations with a human atrial action potential model predicted that the minK38G SNP would slightly prolong the atrial action potential and reduce the frequency for alternans behaviour. In the presence of reduced repolarization reserve, these effects were enhanced and under specific conditions early afterdepolarizations occurred. The minK38G isoform is associated with reduced I(Ks), likely due to decreased KvLQT1 membrane expression. This study reveals a novel amino acid determinant of the minK-KvLQT1 interaction, and if the role of minK38G in AF is confirmed, would suggest mechanistic heterogeneity in genetic determinants of AF.


Genome-wide transcriptome profiling of genes associated with arsenate toxicity in an arsenic-tolerant rice mutant.
The presence of arsenic (As) in polluted environments, such as ground water, affects the accumulation of As in rice grains and causes a serious threat to human health. However, the precise molecular regulations related to As toxicity and tolerance in rice remain largely unknown. In the present study, we developed an arsenic-tolerant type 1 (ATT1) rice mutant by γ-irradiation mutagenesis and performed genome-wide transcriptome analysis for the characterization of As-responsive genes. Toxicity inhibited transcriptional regulation of putative genes involved in photosynthesis, mitochondrial electron transport, and lipid biosynthesis metabolism in wild-type (WT) and ATT1 rice mutant. However, many cysteine biosynthesis-related genes were significantly upregulated in both plants. We also attempted to elucidate the putative genes associated with As tolerance by comparing transcriptomes and identified ATT1-specific transcriptional regulation of genes involved in stress and RNA-protein synthesis. This analysis identified 50 genes that had DNA polymorphisms in upstream regions that differed from those in the exon regions, which suggested that genetic variations in the upstream regions might enhance As tolerance in the mutants. Therefore, the expression profiles of the genes evaluated in this study may improve understanding of the functional roles of As-related genes in response to As tolerance mechanisms and could potentially be used in molecular breeding to limit As accumulation in rice grains.


Natural killer cells in placentation and cancer: Implications for hypertension during pregnancy.
Hypertension during pregnancy is the most common medical condition encountered during gestation. Despite this, knowledge of the mechanisms that underlie the disease and the development of new therapies are limited. Hypertension during pregnancy and some forms of cancer confer an increased risk to the development of cardiovascular disease later in life; one mechanism which may link these conditions is the involvement of natural killer (NK) cells. Whilst immunology and immunotherapy are well-developed areas in oncology; the complex mechanisms of the immune system in health and disease at the maternal-fetal interface are less well-defined. Natural killer (NK) cells have emerged as key immune cells involved in physiology and pathology of pregnancy. These small lymphocytes are present in the decidua (the uterine-specific uNK cells) and are distinct from peripheral NK cells. The uNK cell population plays a vital role in mediating trophoblast invasion and affecting decidual vascular remodelling whereas the role of the peripheral NK cell population during pregnancy is less well-defined. This review will give an overview of NK cell biology followed by a discussion of the current evidence for the role of uterine and peripheral NK cells at the maternal-fetal interface in health and disease. Furthermore, examples of NK cell research from cancer biology will be employed to inform future directions of research. By combining this knowledge from oncology where the field of immunotherapy has now matured into clinical trials; it is hopeful that new mechanisms can be elucidated to generate targets for similar therapeutic strategies for women with hypertensive pregnancies where interventions are needed.


Aspects of a Suspended Bioprinting System Affect Cell Viability and Support Bath Properties.
Suspended hydrogel printing is a growing method for fabricating bioprinted hydrogel constructs, largely due to how it enables nonviscous hydrogel inks to be used in extrusion printing. In this work, a previously developed poly(N-isopropylacrylamide)-based thermogelling suspended bioprinting system was examined in the context of chondrocyte-laden printing. Material factors such as ink concentration and cell concentration were found to have a significant effect on printed chondrocyte viability. In addition, the heated poloxamer support bath was able to maintain chondrocyte viability for up to 6 h of residence within the bath. The relationship between the ink and support bath was also assessed by measuring the rheological properties of the bath before and after printing. Bath storage modulus and yield stress decreased during printing as nozzle size was reduced, indicating the likelihood that dilution occurs over time through osmotic exchange with the ink. Altogether this work demonstrates the promise for printing high-resolution cell-encapsulating tissue engineering constructs, while also elucidating complex relationships between the ink and bath, which must be taken into consideration when designing suspended printing systems.


Effects of the respiratory tract on inhaled materials.
Inhalation exposure is often compared to intravenous or oral routes of administration with regard to the biological fate of inhaled materials. Such comparisons, however, overlook the contribution of respiratory tract enzymes to the metabolic fate and toxicity of inhaled materials. The effect of respiratory tract metabolism on the toxicity of inhaled materials is thought to be substantial for many compounds for the following reasons. (1) High concentrations of xenobiotic metabolizing enzymes occur in the nose and substantial concentrations occur in the lung. (2) The respiratory tract tissues are the first exposed to inhaled materials and are exposed to the highest concentrations (barring tissue specific uptake). (3) The products of respiratory tract metabolism may have different toxicities from those of hepatic metabolism. (4) Tissues at risk to toxic metabolites formed in the respiratory tract are different from those formed in the liver. These four reasons for concluding that respiratory tract metabolism may influence the toxicity of inhaled materials are backed by a solid body of expanding experimental data. Therefore, a complete assessment of the fate of inhaled materials should include assessment of potential contributions of respiratory tract metabolism.


FOXO1-regulated lncRNA CYP1B1-AS1 suppresses breast cancer cell proliferation by inhibiting neddylation.
Overactivated neddylation is considered to be a common event in cancer. Long non-coding RNAs (lncRNAs) can regulate cancer development by mediating post-translational modifications. However, the role of lncRNA in neddylation modification remains unclear. LncRNA cytochrome P450 family 1 subfamily B member 1 antisense RNA 1 (CYP1B1-AS1) expression in breast cancer tissues was evaluated by RT-PCR and TCGA BRCA data. Gain and loss of function experiments were performed to explore the role of CYP1B1-AS1 in breast cancer cell proliferation and apoptosis in vitro and in vivo. Luciferase assay, CHIP-qPCR assay, transcriptome sequencing, RNA-pulldown assay, mass spectrometry, RIP-PCR and Western blot were used to investigate the regulatory factors of CYP1B1-AS1 expression and the molecular mechanism of CYP1B1-AS1 involved in neddylation modification. We found that CYP1B1-AS1 was down-regulated in breast cancer tissues and correlated with prognosis. In vivo and in vitro functional experiments confirmed that CYP1B1-AS1 inhibited cell proliferation and induced apoptosis. Mechanistically, CYP1B1-AS1 was regulated by the transcription factor, forkhead box O1 (FOXO1), and could be upregulated by inhibiting the PI3K/FOXO1 pathway. Moreover, CYP1B1-AS1 bound directly to NEDD8 activating enzyme E1 subunit 1 (NAE1) to regulate protein neddylation. This study reports for the first time that CYP1B1-AS1 inhibits protein neddylation to affect breast cancer cell proliferation, which provides a new strategy for the treatment of breast cancer by lncRNA targeting neddylation modification.


Segmental spinal reflex adaptations associated with chronic ankle instability.
To further understanding of the role that segmental spinal reflexes play in chronic ankle instability (CAI). A 2 x 2 repeated-measures case-control factorial design. The independent variables were ankle group with 2 levels (healthy, CAI) and stance with 2 levels (single, double legged). University research laboratory. Twenty-two participants with CAI and 21 matched healthy controls volunteered. Not applicable. The dependent variables were 2 measures of motoneuron pool excitability: paired reflex depression (PRD) and recurrent inhibition. A 2 x 2 repeated-measures multivariate analysis of variance revealed a significant interaction between group and stance on the linear combination of PRD and recurrent inhibition variables (Wilks lambda=.808, F(2,40)=4.77, P=.014). Follow-up univariate F tests revealed an interaction between group and stance on the PRD (F(1,41)=9.74, P=.003). Follow-up dependent t tests revealed a significant difference between single- and double-legged PRD in the healthy participants (t(20)=-3.76, P=.001) with no difference in CAI participants (t(21)=-0.44, P=.67). Finally, there was a significant difference in recurrent inhibition between healthy (mean, 83.66) and CAI (mean, 90.27) (P=.004). This study revealed that, compared with healthy participants, CAI participants were less able to modulate PRD when going from a double- to a single-legged stance. Additionally, CAI participants showed higher overall levels of recurrent inhibition when compared with healthy matched controls.


Calcium alginate swab versus Bard Parker blade in the diagnosis of microbial keratitis.
A prospective comparative evaluation of Bard Parker blade no. 15 and calcium alginate swab in the collection of corneal material was conducted. The study group included 30 consecutive cases of bacterial (n = 17), fungal (n = 11), and mixed (n = 2) cases of microbial keratitis. The samples collected by blade and swab were processed in an identical manner for viable colony counts. The yields from blade and swab were compared using the proportion test, taking into consideration the mean counts of each organism. The swab yielded significantly greater growth than blade (p = 0.003) in mycotic ulcers. However, the two patients (2/11) who showed no growth by blade but were positive by swab had smears positive and were diagnosed as mycotic ulcers. The difference between the two methods was not significant for bacterial and mixed ulcers. Replacement of blade with calcium alginate swab did not appear to be advantageous for the investigation of infectious keratitis.


Evaluation of chemically modified hydrophobic sago starch as a carrier for controlled drug delivery.
The present investigation deals with the development of controlled release tablets of lamivudine using acetylated sago starch. The acetylated starch was synthesized with acetic anhydride in pyridine medium. The acetylated sago starch was tested for acute toxicity and drug-excipient compatibility study. The formulations were evaluated for physical characteristics like hardness, % friability, % drug content and weight variations. The in vitro release study showed that the optimized formulation exhibited highest correlation (R) value in the case of higuchi kinetic model and the release mechanism study proved that the formulation showed a combination of diffusion and erosion processes. There was a significant difference in the pharmacokinetic parameters (T max, C max, AUC, V d, T 1/2 and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir® which proves the controlled release property of acetylated sago starch.


Carbon nanotube field-effect transistor (CNT-FET)-based biosensor for rapid detection of SARS-CoV-2 (COVID-19) surface spike protein S1.
The large-scale diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important for traceability and treatment during pandemic outbreaks. We developed a fast (2-3 min), easy-to-use, low-cost, and quantitative electrochemical biosensor based on carbon nanotube field-effect transistor (CNT-FET) that allows digital detection of the SARS-CoV-2 S1 in fortifited saliva samples for quick and accurate detection of SARS-CoV-2 S1 antigens. The biosensor was developed on a Si/SiO2 surface by CNT printing with the immobilization of a anti-SARS-CoV-2 S1. SARS-CoV-2 S1 antibody was immobilized on the CNT surface between the S-D channel area using a linker 1-pyrenebutanoic acid succinimidyl ester (PBASE) through non-covalent interaction. A commercial SARS-CoV-2 S1 antigen was used to characterize the electrical output of the CNT-FET biosensor. The SARS-CoV-2 S1 antigen in the 10 mM AA buffer pH 6.0 was effectively detected by the CNT-FET biosensor at concentrations from 0.1 fg/mL to 5.0 pg/mL. The limit of detection (LOD) of the developed CNT-FET biosensor was 4.12 fg/mL. The selectivity test was performed by using target SARS-CoV-2 S1 and non-target SARS-CoV-1 S1 and MERS-CoV S1 antigens in the 10 mM AA buffer pH 6.0. The biosensor showed high selectivity (no response to SARS-CoV-1 S1 or MERS-CoV S1 antigen) with SARS-CoV-2 S1 antigen detection in the 10 mM AA buffer pH 6.0. The biosensor is highly sensitive, saves time, and could be a helpful platform for rapid detection of SARS-CoV-2 S1 antigen from the patients saliva.


Gastrointestinal parasite diversity of South American camelids (Artiodactyla: Camelidae): First review throughout the native range of distribution.
In South America inhabit an endemic group of ungulates adapted to extreme environments: the South American camelids (SAC), a key component of the Andean biocultural heritage. Until today, SAC are the most important factor of Andean economies and social and ritual life. SAC include two wild species, the guanaco (Lama guanicoe) and the vicuña (Vicugna vicugna), and two domestic species, the llama (Lama glama) and the alpaca (Vicugna pacos). Endoparasitosis are one of the most common diseases in SAC, and have great economic and health relevance. Despite this, there is a lack of knowledge on this concern. The main objective of this work was to conduct the first systematic review of the diversity of gastrointestinal parasites of SAC throughout the entire native range of distribution and to identify several gaps in knowledge. The PRISMA protocol was performed and a total of 101 documents were summarized. At least 36 parasitic helminths and five Eimeria spp. were registered. This work highlights the need for a greater number of works to know with more certainty the parasitic fauna of camelids in the past and present, in order to achieve predictions that allow proper management of camelids for their future conservation. Furthermore, concerted research efforts are needed to understand the biology, epidemiology, diagnosis and distribution of the parasitosis of SAC along the entire distribution range to guide conservation decisions.


Impact of personality pathology on psychosocial functioning.
Personality disorders impair social, occupational, leisure, and global functioning more than a significant disorder such as major depressive disorder. Impairment is found in clinical and community populations. Impairment is independent of co-occurring other mental disorders. Impairment is more stable over time than are the diagnoses themselves. Personality traits are also impairing and may be more predictive of outcomes over time, but a hybrid of personality disorder features and normal range personality traits may be the most predictive model. A general, 'transdiagnostic,' self-other severity factor may be important for understanding the relationship of personality pathology and psychosocial functioning over time. The Alternative DSM-5 Model for Personality Disorders may be useful for the study of psychosocial functioning in individuals with personality pathology.


Comparison of tricortical screw fixation versus a modified suture construct for fixation of ankle syndesmosis injury: a biomechanical study.
To assess the viability of using a modified flexible suture implant instead of a tricortical screw for fixation of ankle syndesmosis failures. Randomized biomechanical study. Orthopaedic Research Laboratories at the University of North Carolina at Chapel Hill. Formalin-preserved cadaveric legs were used in pairs. Two holes, 2.5 millimeters in diameter and 7.0 to 10.0 millimeters apart horizontally, were drilled through the fibula and tibia 2.0 centimeters above the tibial plafond. Two strands of Number 5 suture were passed through the holes and tied. Similarly, a 3.5-millimeter tricortical screw was placed on the opposite leg of each pair at 2.0 centimeters. The ankles were tested to failure. This process was repeated at 5.0 centimeters above the tibial plafond. Maximum load and displacement at failure of the suture construct at 2.0 centimeters and at 5.0 centimeters were compared with a tricortical screw at 2.0 centimeters and at 5.0 centimeters. There was no significant difference in strength or displacement between the flexible suture implant and the tricortical screw at either 2.0 centimeters or 5.0 centimeters. The fixations at 5.0 centimeters had significantly increased holding strength over fixations at 2.0 centimeters, and the fixations had significantly greater displacement at 2.0 centimeters than at 5.0 centimeters. This study confirms that flexible syndesmosis repair is a viable option for internal fixation of ankle mortise instability due to syndesmosis rupture.


The morphology of the preimaginal stages of Squamapion elongatum (Germar, 1817) (Coleoptera, Curculionoidea, Apionidae) and notes on its biology.
Data on the morphology of the egg, mature larva (L3) and pupa of Squamapion elongatum (Germar, 1817) are presented. The development cycle of this species lasts 51-54 days: a 12-day egg period, a 30-day larval period, and a 12-day pupal period, on average. The larvae are attacked by parasitic hymenopterans of the superfamily Chalcidoidea.


Pitfalls, fallacies and false positive rates.
True and false positive rates of auditory and visual evoked potentials, as well as multi-modal evoked potentials, were assessed in groups of 30 multiple sclerosis patients and 19 healthy age-matched subjects. Sensitivity (true positive rate) generally proved to be high confirming published reports. False positive rates, which have not been extensively reported previously, proved to be unacceptably high. This held for two different abnormality thresholds (2 or 3 SD above the mean). The explanation for this proved to lie in the nature of an evoked potential test, which may be regarded as a combination of multiple independent components. The combination method, used to label the evoked potential test as normal or abnormal, governs the false positive rate. When the abnormality of at least one component is sufficient to label an evoked potential as abnormal, then the high false positive rate soars with the number of components. To increase the value of clinical evoked potential studies, it is advised that attention is paid to combination methodology, and that true as well as false positive rates should be directly measured.


Laser in situ keratomileusis for treated myopic anisometropic amblyopia in children.
To evaluate the effects of laser in situ keratomileusis (LASIK) in decreasing myopic anisometropia in children with spectacles or contact lens intolerance and its validity in facilitating treatment of resultant myopic anisometropic amblyopia. LASIK was performed in 18 eyes of 18 children having myopic anisometropic amblyopia not successfully treated with the standard amblyopia treatment for 6 months. Children were followed up at 1 week, 1, 2, 6, 12, 18 and 24 months. Postoperative amblyopia therapy was continued with occlusion of the dominant eye for 6 h daily for the first 3 months and then for 4 h per day as long as possible. The mean spherical equivalent refraction in the operated eye had reduced significantly from -9.08 ± 1.86D preoperatively to -0.97 ± 1.16D at 2 years postoperatively. The mean spherical equivalent in the non-operated fellow eye was -1.0 ± 1.15D preoperatively and -2.50 ± 1.15D at 2 years. The mean spherical equivalent myopic anisometropia was -7.75 ± 2.25D preoperatively and -0.50 ± 0.31D at 2 years, representing a 93.5% reduction in myopic anisometropia. The mean regression value was -2.28 ± 1.62D, however, 18 eyes (72%) were within 3.0D of the fellow eye. The mean BCVA was significantly improved from 0.72 ± 0.13 preoperatively to 0.47 ± 0.17 by 2 years after LASIK with amblyopia treatment. LASIK is a safe and effective alternative method for correcting myopic anisometropic amblyopia, especially in children with spectacles or contact lens intolerance, with more better visual acuity and binocular vision.


Cognitive reserve regulates the association between hearing difficulties and incident cognitive impairment evidence from a longitudinal study in China.
Cognitive reserve (CR) can prevent the risk of incident cognitive impairment in the elderly. However, the moderator effects of CR on the link between hearing difficulties (HDs) and the risk of incident cognitive impairment are not well understood. This cohort study obtained data from the Chinese Longitudinal Healthy Longevity Survey from 2008 to 2014. The baseline samples included 6309 participants aged 65 years and older at baseline. Cognitive impairment was assessed using the Chinese version of the Mini Mental State Examination. A composite measure of CR was calculated based on education, occupational complexity, and leisure activities of the participants. The marginal structural model was utilized to investigate whether CR moderates the association between HD and incident cognitive impairment. Odds ratios (ORs) and accompanying 95% confidence intervals (CIs) were calculated. Of the 6309 participants at baseline, 1936 (30.7%) developed cognitive impairment during the 6-year follow-up period and 2562 (40.6%) reported HD. The risk of incident cognitive impairment was 1.90-fold (95% CI 1.69-2.14) for participants developing HD compared to those without. Those with middle CR had lower OR (0.72, 95% CI 0.62-0.82) that further decreased to 0.58 (95% CI 0.49-0.69) for those with high CR. Participants with HD with low CR showed the highest OR (4.32, 95% CI 3.42-5.47). In addition, individuals with HD with low education levels or low complex occupations had the highest risk of incident cognitive impairment. CR moderates the negative association between HD and cognitive function. Education and occupation complexity may be more sensitive proxies for CR.


Impact evaluation of contracting primary health care services in urban Bangladesh.
The Urban Primary Health Care Project (UPHCP) was implemented by the Government of Bangladesh in response to rapid urbanization and growing inequalities in access to and quality of primary health care. The goal of the project was to improve health status of the urban poor living in city corporations and municipalities through the provision of health care services by NGOs that are contracted through public-private partnership. The first phase of the project started in 1998 and the project is currently in its fourth phase covering more urban areas than the first three phases. This study evaluates the impact of the second phase project (UPHCP-II) on health outcomes, mainly child diarrhea, acute respiratory infection, antenatal and postnatal care, skilled birth attendance, breastfeeding prevalence, contraceptive prevalence, sexually transmitted infections, and HIV/AIDS awareness. The effect of the project was estimated through propensity score matching between project and non-project areas comparing baseline and endline surveys over a six-year period from 2006 to 2012. An innovation of this study is the recalibration of the sampling weights that allows the use of these two independent surveys in impact evaluation. Over the six-year period, UPHCP-II improved the health status of the population in project areas compared to non-project areas. The study found significant improvement in health outcomes in terms of reduced diarrhea and acute respiratory infection in children, which explains the downward trend in child mortality rate. Moreover, the project also improved antenatal care and skilled birth attendance. Contraceptive prevalence and HIV/AIDS awareness and avoidance increased, and sexually transmitted infections decreased. UPHCP-II was effective in achieving its health outcome targets, while previous studies show that it was efficient in the delivery of health care and clients were highly satisfied because health facilities were in close proximity, and doctors and staff were perceived as responsive in delivering high quality of care. The results of this study could help inform future design and implementation of urban health interventions that involve contracting primary health care service delivery in Bangladesh and other similar settings.


Quantitative determination of conjugated linoleic acid and polyunsaturated fatty acids in milk with C17:0 as internal marker - Evaluation of different methylation procedures.
Fatty acids are commonly analysed by gas chromatography as their corresponding fatty acid (FA) methyl esters (FAME). For quantitative determination of individual FA an internal standard like C17:0 is necessary. Conjugated FA and polyunsaturated fatty acid (PUFA) represents a challenge in the methylation steps, as they are sensitive to pH changes and oxidation. The present study was carried out to determine the efficiency of different methylation procedures on quantitative determination of conjugated linoleic acid (CLA), PUFA and response of internal standard. The highest response of internal standard was observed for boron trifluoride (BF3)/methanol and methanolic HCl followed by NaOCH3, while cis-9, trans-11 CLA, total CLA and PUFA was higher with methanolic HCl followed by NaOCH3 compared with the BF3 method. These data can be useful for quantitating of milk FA.


Comparative mutational analysis of SARS-CoV-2 isolates from Pakistan and structural-functional implications using computational modelling and simulation approaches.
SARS-CoV-2, an RNA virus, has been prone to high mutations since its first emergence in Wuhan, China, and throughout its spread. Its genome has been sequenced continuously by many countries, including Pakistan, but the results vary. Understanding its genomic patterns and connecting them with phenotypic features will help in devising therapeutic strategies. Thus, in this study, we explored the mutation landscape of 250 Pakistani isolates of SARS-CoV-2 genomes to check the genome diversity and examine the impact of these mutations on protein stability and viral pathogenesis in comparison with a reference sequence (Wuhan NC 045512.2). Our results revealed that structural proteins mainly exhibit more mutations than others in the Pakistani isolates; in particular, the nucleocapsid protein is highly mutated. In comparison, the spike protein is the most mutated protein globally. Furthermore, nsp12 was found to be the most mutated NSP in the Pakistani isolates and worldwide. Regarding accessory proteins, ORF3A is the most mutated in the Pakistani isolates, whereas ORF8 is highly mutated in world isolates. These mutations decrease the structural stability of their proteins and alter different biological pathways. Molecular docking, the dissociation constant (KD), and MM/GBSA analysis showed that mutations in the S protein alter its binding with ACE2. The spike protein mutations D614G-S943T-V622F (-75.17 kcal/mol), D614G-Q677H (-75.78 kcal/mol), and N74K-D614G (-73.84 kcal/mol) exhibit stronger binding energy than the wild type (-66.34 kcal/mol), thus increasing infectivity. Furthermore, the simulation results strongly corroborated the predicted protein servers. Our analysis findings also showed that E, M, ORF6, ORF7A, ORF7B, and ORF10 are the most stable coding genes; they may be suitable targets for vaccine and drug development.


Women's health: pregnancy and childbirth. The use of drugs during pregnancy and lactation.
It is a regulatory fact that only 14 drugs are approved for use during pregnancy; none of them is specifically approved for use in nursing mothers. With the current emphasis on breast feeding, more data describing levels of drugs in fetal blood and drug levels in breast milk are necessary. Some of the pharmacologic properties useful in predicting drug transmission during lactation include lipid solubility, ionization constant, and molecular size (which predisposes a drug to crossing membrane barriers to the fetus and the milk).


Single Agent and Synergistic Activity of Maritoclax with ABT-263 in Nasopharyngeal Carcinoma (NPC) Cell Lines.
The BCL-2 anti-apoptotic proteins are over-expressed in many cancers and hence are attractive therapeutic targets. In this study, we tested the sensitivity of two Nasopharyngeal Carcinoma (NPC) cell lines HK1 and C666-1 to Maritoclax, which is reported to repress anti-apoptotic protein MCL-1 and BH3 mimetic ABT-263, which selectively inhibits anti-apoptotic proteins BCL-2, BCL-XL and BCL-w. We investigated the sensitisation of the NPC cell lines to these drugs using the SYBR Green I assay and 3D NPC spheroids. We report that Maritoclax repressed anti-apoptotic proteins MCL-1, BCL-2, and BCL-XL in a dose- and time-dependent manner and displayed a single agent activity in inhibiting cell proliferation of the NPC cell lines. Moreover, combination of Maritoclax and ABT-263 exhibited synergistic antiproliferative effect in the HK1 cells. Similar results were obtained in the 3D spheroids generated from the HK1 cells. More notably, 3D HK1 spheroids either treated with single agent Maritoclax or combination with ABT-263, over 10 days, did not develop resistance to the treatment rapidly. Collectively, the findings illustrate that Maritoclax as a single agent or combination with BH3 mimetics could be potentially useful as treatment strategies for the management of NPC.


Pinning of a ferroelectric Bloch wall at a paraelectric layer.
The phase-field simulations of ferroelectric Bloch domain walls in BaTiO3-SrTiO3 crystalline superlattices performed in this study suggest that a paraelectric layer with a thickness comparable to the thickness of the domain wall itself can act as an efficient pinning layer. At the same time, such a layer facilitates the possibility to switch domain wall helicity by an external electric field or even to completely change the characteristic structure of a ferroelectric Bloch wall passing through it. Thus, ferroelectric Bloch domain walls are shown to be ideal nanoscale objects with switchable properties. The reported results hint towards the possibility to exploit ferroelectric domain wall interaction with simple nanoscale devices.


Huannao Yicong decoction ameliorates cognitive deficits in APP/PS1/tau triple transgenic mice by interfering with neurotoxic interaction of Aβ-tau.
Huannao Yicong decoction (HYD) has been used in the study of AD for many years, which consists of Polygonum multiflorum Thunb., Panax ginseng C.A.Mey., Acorus gramineus Aiton, Coptis chinensis Franch., and Conioselinum acuminatum (Franch.) Lavrova. Previous studies have found that HYD could reduce β-Amyloid (Aβ) deposition and tau hyperphosphorylation which are the two critical pathological factors of AD. However, the mechanism of the neurotoxic interaction between Aβ and tau in AD remains unclear. Thus, the underlying mechanisms for HYD improving cognitive function of AD by interfering with the neurotoxic interaction between Aβ and tau remain to be explored. The main objective of this study is to clarify the specific mechanisms of HYD on interfering with the neurotoxic interaction between Aβ and tau of AD both in vivo and in vitro. APP/PS1/tau triple transgenic mice were randomly divided into 4 groups, namely model group, memantine group, HYD low-dose group (HYD-L), and HYD high-dose group (HYD-H) with 28 mice in each group, while 28 C57BL/6J mice as the control group. Gavage was applied to all the mice daily for 24 weeks. SH-SY5Y model cells overexpressing Aβ and tau proteins as the intervention object in vitro experiments. Morris water maze was used to observe the learning and memory ability of APP/PS1/tau mice. Aβ deposition was detected by immunohistochemistry, and the levels of Aβ1-40 and Aβ1-42 were detected by enzyme-linked immunosorbent assay (ELISA). Neurofibrillary tangles (NFTs) were observed by silver staining and the levels of phosphorylated tau proteins were detected by Western blot. The GSK-3β and CDK-5 mRNA expression were detected by real-time polymerase chain reaction (RT-PCR). Besides, the levels of PSD95, GluR1, NR2A, and NR2B were detected by Western blot. Meanwhile, cell experiments were performed to further verify the effect of HYD on tau phosphorylation related kinases (GSK-3β, CDK-5, and PP2A), which further to clarify the mechanism of HYD intervention on the neurotoxic interaction between Aβ and tau. HYD improved the learning and memory ability of APP/PS1/tau mice. HYD decreased the levels of Aβ1-40 and Aβ1-42 and inhibited tau hyperphosphorylation, which reduced Aβ deposition and NFTs forming. In addition, HYD inhibited the activity of kinases GSK-3β and CDK-5, and enhancing the activity of kinase PP2A. Moreover, HYD inhibited the overexpression of NR2A and NR2B, and increased the expression of GluR1 and postsynaptic density protein-95 (PSD95). HYD can improve the cognitive deficits by interfering with the neurotoxic interaction between Aβ and tau. In addition, HYD can inhibit the overactivation of NMDARs and increase the levels of GluR1 and PSD95, which may play a role in alleviating neuronal excitotoxicity and improving synaptic function.


For debate: should observational clinical studies require ethics committee approval?
All forms of management in medicine involve weighing up: (1) the potential benefits or efficacy of treatment (2) the potential side effects of treatment and (3) the costs or cost-effectiveness of treatment. It is well established that the randomised control trial (RCT) is the gold standard for determining treatment efficacy and it is obvious why RCTs should be subjected to ethical screening. However, RCTs are not the best methodology for every study, particularly as they are so expensive to conduct. Observational studies are particularly valuable for studying side effects and cost-effectiveness of treatment and still have value (albeit of a lesser quality) in assessing treatment efficacy. Most observational clinical studies are not ethically sensitive and, if it is agreed that therefore ethics committee screening is therefore not required for these studies, they can be completed at low cost with minimal need for industry sponsorship. Universal ethics committee requirements for all observational clinical papers would act as an unnecessary barrier to obstruct the publication of useful studies. Paradoxically, the need in many cases to seek industry funding to cover the extra expense for such a requirement would probably make observational studies less ethically sound.


Proteomic-based identification of APCS as candidate protein for diagnosis of patients exhibiting anti-tubercular drug induced liver injury.
Traditional markers evaluate anti-tubercular drug-induced liver injury (AT-DILI). However, these markers have certain limitations and studies are in progress to characterize AT-DILI at an early stage. In the present study, 40 patients were categorized and equally distributed into healthy controls, newly diagnosed tuberculosis (TB), TB without hepatotoxicity and TB with hepatotoxicity groups based on their conventional liver function tests. Relative protein quantification was performed on depleted pooled serum samples of each representative group by LC-MS/MS, and validation of shortlisted protein was done by ELISA. Levels of all analysed biochemical parameters showed a statistical increment in the hepatotoxicity group compared to the other three groups, representing AT-DILI. Comparative proteomic analysis between TB with hepatotoxicity versus TB without hepatotoxicity groups highlighted 24 significant differentially expressed proteins, including PROS1, KNG1, CFH, LCAT, APCS and ADIPOQ. Identified proteins were involved in complement activation, triglyceride-rich lipoprotein particle remodelling and pathways comprising complement, coagulation cascades and cholesterol metabolism. Based on functional relevance, the serum amyloid P component (APCS) was shortlisted for validation, and it showed a similar trend as observed in the discovery phase with 100% sensitivity and 87% specificity; however, findings need exploration in larger cohorts.


GeMprospector--online design of cross-species genetic marker candidates in legumes and grasses.
The web program GeMprospector (URL: http://cgi-www.daimi.au.dk/cgi-chili/GeMprospector/main) allows users to automatically design large sets of cross-species genetic marker candidates targeting either legumes or grasses. The user uploads a collection of ESTs from one or more legume or grass species, and they are compared with a database of clusters of homologous EST and genomic sequences from other legumes or grasses, respectively. Multiple sequence alignments between submitted ESTs and their homologues in the appropriate database form the basis of automated PCR primer design in conserved exons such that each primer set amplifies an intron. The only user input is a collection of ESTs, not necessarily from more than one species, and GeMprospector can boost the potential of such an EST collection by combining it with a large database to produce cross-species genetic marker candidates for legumes or grasses.


[Obstruction of the venae cavae: surgical considerations (author's transl)].
In cases of obstruction of the superior or inferior vena cava--or of both the caval veins--it is always necessary to find out whether surgical therapy is indicated. In relatively rare cases it is possible to achieve better results by means of operative treatment than with conservative therapy only.


Spatial profiling of the microenvironment reveals low intratumoral heterogeneity and STK11-associated immune evasion in therapy-naïve lung adenocarcinomas.
Intratumoral heterogeneity was found to be a significant factor causing resistance to lung cancer therapies, including immune checkpoint blockade. Lesser is known about spatial heterogeneity of the tumor microenvironment (TME) and its association with genetic properties of the tumor, which is of particular interest in the therapy-naïve setting. We performed multi-region sampling (2-4 samples per tumor; total of 55 samples) from a cohort of 19 untreated stage IA-IIIB lung adenocarcinomas (n = 11 KRAS mutant, n = 1 ERBB2 mutant, n = 7 KRAS wildtype). For each sample the expression of 770 immunooncology-related genes was analyzed using the nCounter platform, while the mutational status was determined by hybrid capture-based next-generation sequencing (NGS) using a large panel covering more than 500 genes. Global unsupervised analyses revealed clustering of the samples into two groups corresponding to a 'hot' or 'cold' immunologic tumor contexture based on the abundance of immune cell infiltrates. All analyzed specific immune cell signatures (ICsig) showed a significantly higher intertumoral than intratumoral heterogeneity (p < 0.02), as most of the analyzed cases (14/19) showed a very homogenous spatial immune cell profile. PD-L1 exhibited a significantly higher intertumoral than intratumoral heterogeneity (p = 1.03e-13). We found a specific association with 'cold' TME for STK11 (11/14, p < 0.07), but not KRAS, TP53, LRP1B, MTOR, U2AF1 co-mutations, and validated this finding using The Cancer Genome Atlas (TCGA) data. Early-stage lung adenocarcinomas show considerable intertumoral, but limited intratumoral heterogeneity, which is clinically highly relevant as assessment before neoadjuvant treatment is based on small biopsies. STK11 mutations are specifically associated with a 'cold' TME, which could affect the efficacy of perioperative immunotherapy.


[Epidemiology of infectious acute diarrhoea in France and Europe].
Acute infectious diarrhoea can be linked to various pathogens among which viruses are responsible for more than a half cases. Rotaviruses and caliciviruses are the most frequently encountered, in close to 60 % of viral gastroenteritis. Rotaviruses account for more than 50 % of severe diseases and caliciviruses, especially norovirus are responsible for less severe sporadic gastroenteritis and water-or food- borne epidemics. Astroviruses and adenoviruses are minority, excepted for immunocompromised patients. Viral or Bacterial and viral co- infections are frequent (up to 15 %). To date, the first rotavirus vaccine assays did not reveal any shift from a viral genus to another, such as calicivirus or adenovirus, according to the fact that epidemiologic features of these viruses are quite different. Progress in viral diagnosis and genotyping enabled to analyse viral diversity and to follow viral recombination events, and emergence of new variants that could propagate among various countries. This dynamic evolution that concerns not only Europe but also developing countries should be carefully surveyed at the era of rotavirus vaccination.


White matter maturation is associated with the emergence of Theory of Mind in early childhood.
The ability to attribute mental states to other individuals is crucial for human cognition. A milestone of this ability is reached around the age of 4, when children start understanding that others can have false beliefs about the world. The neural basis supporting this critical step is currently unknown. Here, we relate this behavioural change to the maturation of white matter structure in 3- and 4-year-old children. Tract-based spatial statistics and probabilistic tractography show that the developmental breakthrough in false belief understanding is associated with age-related changes in local white matter structure in temporoparietal regions, the precuneus and medial prefrontal cortex, and with increased dorsal white matter connectivity between temporoparietal and inferior frontal regions. These effects are independent of co-developing cognitive abilities. Our findings show that the emergence of mental state representation is related to the maturation of core belief processing regions and their connection to the prefrontal cortex.


The role of the platelet in coagulation and clinical thrombotic events.
There have been exciting advances in our understanding of platelet function in recent years. Platelet physiology, drugs that inhibit platelet function, and the current evidence supporting the use of platelet-inhibiting drugs in the prevention of clinical thrombotic events are reviewed.


[Critical study of the hemodynamic status during anesthesia].
Physicians must choose the anaesthetics for their patients and select the methods to cheek their haemodynamic status. Experimental works do not always bring sufficient information to help them in their daily practice. Circulatory reaction to a pharmacodynamic agent is diffuse and non-specific. Some examples drawn from theoretical considerations and practical situations support this view. The difficulty of assessing the actual damage caused by one apparent variation still remains. On the other hand, haemodynamic indices such as PA, CVP, dP/dt are composed of elementary data that are interdependent; so indices are interdependent, too. A puzzling fact is that depressing anaesthetics can initiate severe haemodynamic crisis, generally badly tolerated by tissues, but better tolerated by myocardium which is not definietely altered if the anoxia inflicted is accompanied by a real decrease in cardiac work. This explains the often slight effect of short anesthetic overdosage. Previous haemodynamic variations to be countered relative to anaesthesia are not really known. Biochemistry of the venous coronary blood does not yet bring striking features in this field.


Motor development in individuals with congenital adrenal hyperplasia: strength, targeting, and fine motor skill.
This study investigated early androgen influence on the development of human motor and visuomotor characteristics. Participants, ages 12-45 years, were individuals with congenital adrenal hyperplasia (CAH), a disorder causing increased adrenal androgen production before birth (40 females, 29 males) and their unaffected relatives (29 females, 30 males). We investigated grip strength and visuomotor targeting tasks on which males generally outperform females, and fine motor pegboard tasks on which females generally outperform males. Physical characteristics (height and weight) were measured to explore whether body parameters could explain differences in motor skills. Females with CAH were stronger and showed better targeting than unaffected females and showed reduced fine visuomotor skill on one pegboard measure, with no difference on the other. Males with CAH were weaker than unaffected males in grip strength but did not differ on the targeting or pegboard measures. Correction for body size could not explain the findings for females, but suggests that the reduced strength of males with CAH may relate to their smaller stature. Further, the targeting advantage in females with CAH persisted following adjustment for their greater strength. Results in females support the hypothesis that androgen may masculinize, or promote, certain motor characteristics at which males excel, and contribute to defeminization of certain fine motor characteristics at which females excel. Thus, these data suggest that organizational effects of androgens on behavior during prenatal life may extend to motor characteristics and may contribute to general sex differences in motor-related behaviors; however, alternative explanations based on activational influences of androgen or altered experiential factors cannot be excluded without further study.


Renin concentration after prolonged cold storage of human plasma.
The plasma renin concentration (PRC3.3) measured biologically or radioimmunologically after acid treatment of plasma at pH 3.3, did not change significantly during storage of human plasma at -20 degrees C for 1 year. This is completely in contradiction with the increase in plasma renin activity reported by some authors.


Population density mediates induced immune response, but not physiological condition in a well-adapted urban bird.
Thriving under high population density is considered a major feature of urban exploiter species. Nevertheless, population density appears to be a surprisingly overlooked factor in urban ecology studies. High population numbers observed in urban species might promote pathogen transmission and negatively affect health or condition, thus requiring investments in immunocompetence. The feral pigeon Columba livia domestica is an example of a successful city-dweller, found in great abundance in large cities across the globe. We investigated the effects of population density on induced immune response (phytohaemagglutinin skin test) and body condition (blood haemoglobin concentration and size-corrected body mass) in 120 feral pigeons, captured along population density gradient in Łódź (central Poland). We found that stronger immune response was associated with higher population density, but was not related to physiological condition and physiological stress (heterophil/lymphocyte ratio). Moreover, condition indices were not associated with population density. However, since pigeon population density was highly correlated with the level of habitat urbanization, we cannot exclude that any density-dependent effects may be mediated by habitat variation. Our results indicate that urban environment, via population density, might exert different selective pressures on immunocompetence and body condition in this successful urban exploiter.


[Origin of Kupffer macrophages in the regenerating liver].
Male Wistar rats were injected intraperitoneally with H3-thymidine (5 muC/g). Two thirds of the liver was removed one hour later. Sham operated animals served as control. A moderate elevation of the labeled nuclei indices of hepatocytes (LNI) was seen by the third hour, increased significantly by the ninth, and especially by the 24th hour after the operation. The indices decreased by the 48th hour after partial hepatectomy. In 3 hours the LNI was 10 times higher than in the control; in 9 hours it reached the maximum, decreasing by the 24th and 48th postoperative hours. The origin of Kupffer's macrophages in the regenerating liver is discussed.


DRAINAGE RETINOTOMY IS A RISK FACTOR FOR SURGICAL FAILURE AFTER PARS PLANA VITRECTOMY IN PATIENTS WITH PRIMARY UNCOMPLICATED RHEGMATOGENOUS RETINAL DETACHMENT.
To identify risk factors for recurrent retinal detachment after uncomplicated pars plana vitrectomy in patients with primary rhegmatogenous retinal detachment (RRD). This single-center retrospective study included patients with primary RRD who underwent 23-gauge and 25-gauge pars plana vitrectomy at Hiroshima University Hospital between January 2016 and May 2021. All patients had ≥3 months of follow-up. Patients were excluded if they had preoperative proliferative vitreoretinopathy worse than Grade C1; giant retinal tears; tractional, exudative, or traumatic retinal detachment; or the use of perfluorocarbon liquid. Factors that influenced RRD treatment outcome and postoperative complications were evaluated. We analyzed 519 eyes of 509 patients who underwent pars plana vitrectomy for primary RRD. The primary and final success rates were 93.8% and 99.8%, respectively. Drainage retinotomy was a risk factor for surgical failure in both multivariate analysis (odds ratio 2.36, 95% confidence interval 1.08-5.15, P = 0.0314) and a propensity score-matching analysis (odds ratio 3.20, 95% confidence interval 1.14-9.04, P = 0.0277). Postoperative epiretinal membrane was associated with drainage retinotomy in multivariate analysis (odds ratio 1.93, 95% confidence interval 1.04-3.57, P = 0.0358). The avoidance of drainage retinotomy during small-gauge pars plana vitrectomy in patients with RRD may lead to better surgical success and less frequent epiretinal membrane formation.


Reduction of quinones and phenoxy radicals by extracellular glucose dehydrogenase from Glomerella cingulata suggests a role in plant pathogenicity.
The plant-pathogenic fungus Glomerella cingulata (anamorph Colletotrichum gloeosporoides) secretes high levels of an FAD-dependent glucose dehydrogenase (GDH) when grown on tomato juice-supplemented media. To elucidate its molecular and catalytic properties, GDH was produced in submerged culture. The highest volumetric activity was obtained in shaking flasks after 6 days of cultivation (3400 U l⁻¹, 4.2 % of total extracellular protein). GDH is a monomeric protein with an isoelectric point of 5.6. The molecular masses of the glycoforms ranged from 95 to 135 kDa, but after deglycosylation, a single 68 kDa band was obtained. The absorption spectrum is typical for an FAD-containing enzyme with maxima at 370 and 458 nm and the cofactor is non-covalently bound. The preferred substrates are glucose and xylose. Suitable electron acceptors are quinones, phenoxy radicals, 2,6-dichloroindophenol, ferricyanide and ferrocenium hexafluorophosphate. In contrast, oxygen turnover is very low. The GDH-encoding gene was cloned and phylogenetic analysis of the translated protein reveals its affiliation to the GMC family of oxidoreductases. The proposed function of this quinone and phenoxy radical reducing enzyme is to neutralize the action of plant laccase, phenoloxidase or peroxidase activities, which are increased in infected plants to evade fungal attack.


The effect of benzodiazepines and flumazenil on motor cortical excitability in the human brain.
In the present study, the effects of benzodiazepines (diazepam) were evaluated in terms of cortical excitability changes, as tested with transcranial magnetic simulation (TMS). In particular, analyzed were drug-induced changes regarding two selected parameters of TMS: (1) the cortical excitability threshold and (2) the silent period duration (SP). For this purpose, we evaluated the effects of long-term therapy with diazepam in the patients affected by anxiety disorders and the changes induced by single oral doses of diazepam in both healthy controls and patients. In addition, we tested cortical excitability changes in two 'extreme conditions' where a considerable concentration of serum benzodiazepine-like activity was reached, as represented by diazepam overdose and idiopathic recurrent stupor (IRS). In both groups of patients, a significant increment of motor threshold was found, while in the overdose patients, the SP was also increased. The administration of flumazenil in these two conditions was followed by a prompt reversal effect, consisting of a return to normal cortical excitability parameters. The long-term usage of diazepam in patients with anxiety disorders is associated with significantly increased threshold; the increased value of these parameters was temporarily further enhanced by the administration of a single oral dose of diazepam, which, in normal control subjects, is not associated with changes of cortical excitability. The results of this study reveal that different physio-pathological conditions induced by the influence of benzodiazepine and its antagonist are reflected in excitability changes which attest to the involvement and modification of cortical GABAergic activity.


Metal-Ligand Cooperativity in MnI -Catalysed N-Formylation of Secondary Amides and Lactams Using CO2 at Room Temperature.
A MnI catalyst featuring redox-active tridentate phenalenyl (PLY) ligand has been used for catalytic N-formylation of secondary amides and lactams under 1 atm CO2 as a C1 source at room temperature for the first time. The protocol is applicable to a wide range of secondary amides including heterocycles, bio-active cinnamide derivatives and the diversification of therapeutic molecules. In-depth mechanistic investigations based on experimental outcomes and DFT calculations suggested an unconventional metal-ligand cooperation, where a ligand-centred radical plays a crucial role in initiating the reaction process.


The emergence of multidisciplinary teams for interagency service delivery in europe: is historical institutionalism wrong?
In Europe, a well-known problem is the coordination of interagency service delivery to independently living older persons, disabled persons or persons suffering from chronic illness. Coordination is necessary in order for the users to receive services at the appropriate time and place. Based on historical institutionalism, which focuses on the path dependency of the development of government policy and organizational and professional rules, it can be stated that coordination requires organizational models or other solutions that fit the characteristics of the context ('configuration') for which the solution is intended. The western European countries have different configurations. Remarkably, across these countries, we see the emergence of multidisciplinary teams as a solution to the problem of coordination. Consequently, if we take the above statement to mean that a solution should fit all the configuration's characteristics, we must reject the statement. However, when we assume that a solution should fit particular configurational characteristics, we must not. We take the second position and we argue that multidisciplinary teams have emerged because they fit one particular feature that is similar in the countries: professionalism and professional fragmentation.


Revenge of the phages: defeating bacterial defences.
Bacteria and their viral predators (bacteriophages) are locked in a constant battle. In order to proliferate in phage-rich environments, bacteria have an impressive arsenal of defence mechanisms, and in response, phages have evolved counter-strategies to evade these antiviral systems. In this Review, we describe the various tactics that are used by phages to overcome bacterial resistance mechanisms, including adsorption inhibition, restriction-modification, CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems and abortive infection. Furthermore, we consider how these observations have enhanced our knowledge of phage biology, evolution and phage-host interactions.


Regiodivergent Conversion of Alkenes to Branched or Linear Alkylpyridines.
Herein we report a practical protocol for the visible-light-induced regiodivergent radical hydropyridylation of unactivated alkenes using pyridinium salts. This approach provides a unified synthetic platform to control the regioselectivity of the synthesis of linear or branched C4-alkylated pyridines. A remarkable selectivity switch from the anti-Markovnikov to the Markovnikov product can be achieved by the addition of tetrabutylammonium bromide. The versatility of this protocol is further demonstrated based on the late-stage functionalization in pharmaceuticals.