Risk Factors Related to Lower Limb Edema, Compression, and Physical Activity During Pregnancy: A Retrospective Study.
The aim of the article was to assess risk factors and to analyze methods applied in the prevention and treatment of lower limb edema in pregnant women with a particular focus on compression therapy and exercise. Fifty-four women during the early 24-hour period following delivery were assigned to two groups-either to a group with swellings of lower limbs during pregnancy, located mostly in the region of feet and lower legs (Group A, n = 42), or to a group without edema (Group B, n = 12). Two subgroups, namely A1 and A2, were additionally distinguished in Group A. Compression therapy that consisted in wearing circular-knit compression garments, usually at compression level 1 (ccl1), with three cases of compression level 2 (ccl2) was applied only in Group A1 (n = 18 women). The analysis has led to a conclusion that there is a link between the occurrence of edema during pregnancy on the one hand and the pregravidity episodes of venous conditions (vascular insufficiency and thrombosis, p < 0.05) and the lack of physical exercise during pregnancy (p = 0.01) on the other hand. However, interdependence between the occurrence of edema and the number of times a female had been pregnant, physical activity before gravidity, or body mass index before gravidity has not been identified. Only 33% of the analyzed women applied compression therapy during pregnancy; a half of them continued to apply compression during the postpartum period. Compression therapy in combination with proper physical exercises appears to be an effective means to prevent and treat venous thrombosis and lower limb edema in pregnant women, yet further research in line with the principles of evidence-based medicine is required.


Protocol-directed versus physician-directed weaning from noninvasive ventilation: the impact in chronic obstructive pulmonary disease patients.
Noninvasive ventilation (NIV), a technique widely used in intensive care units (ICUs), eliminates the need for many patients in respiratory failure to undergo intubation. However, few articles have described how to wean patients from NIV. Herein, we put forward a protocol to be performed by respiratory therapists to wean patients from NIV. A prospective, randomized, controlled trial was performed in a respiratory ICU of a teaching hospital. Respiratory therapists screened patients daily. In the protocol-directed weaning group, the weaning attempt was initiated according to the protocol. In the physician-directed weaning group, the weaning attempt was initiated according to physicians' orders. At randomization, patients in the two groups had similar clinical characteristics. A total of 73 patients were successfully weaned from NIV (37 in the protocol-directed group and 36 in the physician-directed group). The preponderance of them (64%) was chronic obstructive pulmonary disease patients. Compared with physician-directed weaning, protocol-directed weaning reduced the duration of NIV (4.4 ± 2.5 days vs. 2.6 ± 1.5 days, respectively, p < 0.001) and the duration of the ICU stay (8.1 ± 5.5 days vs. 5.8 ± 2.7 days, respectively, p = 0.02). In the protocol-directed group, the successful weaning rate was 57%, 27%, 13%, 0%, and 3% on the 1st, 2nd, 3rd, 4th, and 5th days after randomization, respectively. Protocol-directed weaning reduces the duration of NIV and the duration of the ICU stay. II.


HLA-DR antigen expression in primary melanomas of the skin.
Ninety-three primary malignant melanomas of the skin were typed immunohistologically for the expression of HLA-DR on tumor cells. HLA-DR-positive stroma cells were HLA-DR-negative or only locally positive in most cases. In 36 (39%) of the lesions more than 10% of the tumor cells were stained by two monoclonal antibodies against the nonpolymorphic portion of HLA-DR. HLA-DR-positive tumor cells were often accumulated at the advancing front of the melanoma. The occurrence of HLA-DR-positive tumor cells was related to tumor thickness and level of invasion. Substantial numbers of HLA-DR-positive tumor cells were found in half of the tumors thicker than 1.5 mm and in only 18% of flatter lesions. The highest percentage of HLA-DR-positive tumors was found in the group of melanomas invading the reticular dermis (level IV). The majority of tumors (18/24) that had metastasized within an observation period of 0-32 months were HLA-DR-positive. Regarding the mononuclear cell infiltrate, no correlation between the degree of overall infiltrate and the expression of HLA-DR by the tumor cells was found. The infiltrate within the tumor, however, was more often marked in HLA-DR-positive than in HLA-DR-negative melanomas.


Production of auto-anti-idiotype antibody during the normal immune response. XIV. Evidence for the antigen-independent operation of the idiotype network.
We have previously shown that that idiotype (Id) repertoire expressed by old mice is different from that of young mice after immunization with trinitrophenylated Ficoll. Older mice also produce more auto-anti-Id antibodies than do young mice. Mice surviving a normally lethal dose of radiation (800 rads) as result of partial shielding of their bone marrow slowly recover immune function, after the repopulation of their peripheral lymphoid system by bone marrow precursor cells. Aged mice subjected to such a procedure produce low auto-anti-Id responses, like those of young mice. However, transfer of splenic T cells from old donors into such mice increases the magnitude of the auto-anti-Id response. In the present studies, we show that the age-related shift in Id expression is also determined by the age of the donor T cells. Furthermore, we show in serial cell transfer studies that the peripheral T-cell population of old mice modifies the level of the auto-anti-Id response in the absence of antigen. The results thus provide evidence for the normal, in vivo, operation of an Id-anti-Id network between B and T lymphocytes.


Potential and polarization measurements in vivo of oral galvanism.
Galvanic currents within the oral cavity may have harmful effects on biological tissues. In the present work 16 patients with different kinds of oral and other discomfort and pain which they attributed to oral galvanism were investigated. The potential and polarization of each metal restoration within reach of a platinum probe were measured versus a reference electrode. A recording of these measured values permits a calculation of the currents which may pass between the teeth. A control group of patients with no subjective symptoms of galvanism in the oral cavity was also investigated. The results of the electrochemical measurements showed that conditions for oral galvanism existed within the individuals of the patient group as well as within the control group. One remarkable observation was that the metallic restorations often consisted of different electrically isolated areas with different electrochemical properties. This and other factors influencing oral galvanism are discussed.


Design of libraries targeting protein-protein interfaces.
TARGETING PPIS: A novel strategy for designing libraries targeting protein-protein interfaces enabled us to identify diverse chemical entry points to interact with therapeutic targets for which conventional screening libraries delivered no or only few hit structures. The concept was experimentally validated by early hit evaluation in biochemical screens and early ADMET profiling.


Percutaneous endoscopic gastrostomies: a prospective evaluation and review of the literature.
The results of the first 55 consecutive percutaneous endoscopic gastrostomies (PEGs) that were performed over an 18-month period in a tertiary care center are presented. We followed these cases prospectively to assess the morbidity, mortality, staff acceptance, short-and long-term complications, and cost effectiveness of the technique. Fifty-one (93%) were successful with no mortality. Long-term morbidity included 6/55 (11%) tube extrusions; 5/55 (9%) cellulitis around the catheter site; 5/55 (9%) aspiration pneumonias; and 2/55 (3.6%) clogged tubes requiring replacement. Morbidity was considered minor and easily dealt with in all but five instances (9%) where more prolonged treatment was required. A review of the literature including other techniques used for percutaneous gastrostomy is also presented. It is concluded that percutaneous gastrostomies are relatively safe, cost-effective, and should be given first consideration for long-term enteral therapy in appropriate patients.


Influence of postextraction substrate aging on the microtensile bond strength of a dental adhesive system.
To investigate the effect of postextraction substrate aging on the microtensile bond strength (muTBS) of an adhesive system (Excite). Sixty sound human third molars were extracted for orthodontic purposes and prepared after the following storage periods in distilled water at 37 degrees C (n = 10): G1 - 1 h; G2 - 24 h; G3 - 7 days; G4 - 30 days; G5 - 1 year; G6 - 2 years. The occlusal surfaces were removed using diamond disks to expose middle dentin and a standardized smear layer was created by polishing with wet 600-grit sandpaper. The adhesive system was applied according to the manufacturer's instructions, and a resin composite block (5 mm in height, Tetric Ceram shade A2/Ivoclar Vivadent) was built in 1-mm increments, each one being light cured for 40 s (600 mW/cm2). After storage in distilled water at 37 degrees C for 24 h, teeth were sectioned to obtain stick-shaped specimens with a cross-sectional area of approximately 0.7 +/- 0.2 mm2. Specimens were submitted to muTBS test in a Kratos universal testing machine at a crosshead speed of 0.5 mm/min. Data were statistically analyzed using one-way ANOVA at a significance level of 5% (p < 0.05) The mean muTBS in MPa +/- SD were: G1 = 47 +/- 3.1; G2 = 42 +/- 5.1; G3 = 41 +/- 6.4; G4 = 43 +/- 9.8; G5 = 40 +/- 7.0; G6 = 52 +/- 5.7. No statistically significant difference was found among experimental groups. Human teeth stored for long periods of time can be used to determine the in vitro muTBS of one-bottle adhesive systems.


The rise and fall of one unit's patient satisfaction scores.
Lessons may be learned from analyzing how a medical unit dramatically improved patient satisfaction scores, only to have the scores drop in future years. This article describes one hospital's experience in improving patient satisfaction by employing a parallel learning structure that promoted innovation and employee involvement. The reasons that gains in patient satisfaction and quality were not sustained are analyzed, and change management theory is used to explain what healthcare managers can do to prevent such capitulation in their own improvement efforts.


New aspects of the alpha-helix to beta-sheet transition in stretched hard alpha-keratin fibers.
The putative transformation of alpha-helices into beta-sheets has been studied for more than 50 years in the case of hard alpha-keratin. In a previous study of stretched keratin fibers, we specified the conditions for beta-sheet appearance within horsehair: the formation of beta-sheets requires at least 30% relative humidity. However, this phenomenon was observed in the whole tissue. Then there was no clear chemical identification of the beta-sheets (keratin or matrix proteins) and the exact location of the beta-sheets across the fiber could not be specified. In this study, using wide-angle x-ray scattering and high spatial resolution infrared microspectroscopy, we could determine and characterize the structural elements across hair sections stretched in water, which provides new information about the aforementioned transition. Our results show that the process can be split into three steps: 1), unraveling of the alpha-helical coiled-coil domains, which starts at roughly 5% macroscopic strain; 2), further transformation of the unraveled coiled-coils into beta-sheet structures, which occurs above roughly 20% macroscopic strain; and 3), spatial expanding of the beta-structured zones from the sample center to its periphery.


Relational Aggression, Victimization and Self-Concept: Testing Pathways from Middle Childhood to Adolescence.
When studying adolescent development, it is important to consider two key areas that are salient for teens, which are self-concept and peer relations. A secondary analysis of the National Institute of Health and Human Development Study of Early Child Care and Youth Development was conducted to examine the prospective bidirectional associations between self-concept and peer relations. To date, how social development broadly and peer relations in particular (e.g., relational aggression and victimization) affect self-concept domains is not fully understood. Using a large sample (N = 1063; 532 girls; M = 11.14 years; SD = .59) with multiple informants, the present study examined whether fifth grade relational aggression and sixth grade relational victimization was associated with adolescent self-concept in three key domains (i.e., academic, sports, physical appearance). A significant direct effect emerged, such that relational aggression in middle childhood was associated with decreases in academic self-concept and increases in sports self-concept in adolescence. Analyses also revealed that having higher levels of domain specific self-concept led to decreases in relational aggression across the transition to adolescence. The findings highlight the importance of examining bidirectional prospective associations between relational aggression, relational victimization, and domain specific self-concept. Implications for future research and clinical intervention are discussed.


Mirror-image asymmetry in monozygotic twins with kabuki syndrome.
Kabuki syndrome (OMIM 147920) is a rare disorder characterised by moderate intellectual disability, growth retardation, microcephaly and characteristic facial dysmorphic features which comprise long palpebral fissures, eversion of the lateral third of the eyelids and arched eyebrows with lateral sparseness. Mutations in MLL2 are the most frequent cause of this disorder. More than 100 MLL2 point mutations have been reported, but large intragenic deletions comprising one or more exons have not yet been identified. We report on a pair of monozygotic twin brothers in whom a deletion of 2 neighbouring exons was detected. The twins had the characteristic facial features of Kabuki syndrome, and they suffered from microcephaly, cleft lip and palate and congenital heart disease. Cleft lip and palate were left-sided in the first twin and right-sided in the second twin, i.e. they represented a mirror-image asymmetry. The intragenic deletion in these brothers broadens the spectrum of MLL2 mutations, and they provide a rare example of mirror-image asymmetry of congenital malformations in monozygotic twins.


Simultaneous determination of B-vitamins and ascorbic acid in multi-vitamin preparations by reversed-phase HPLC.
The tedious and time consuming methods employed for the analysis of individual B-vitamins can now be replaced by ion-pair reversed-phase high-performance liquid chromatographic (HPLC) methods. This laboratory has previously reported the simultaneous determination of eight water-soluble vitamin standards that is, B1, B2, B6, B12, C, niacin, niacinamide and folic acid. The proposed isocratic HPLC method, employing 3 channels of detection, adequately separated all eight vitamins in less than 20 minutes. This study reports another phase of the project whereby the method was employed for the analysis of pharmaceutical preparations. Different extraction procedures were first evaluated, namely acid, acid plus enzyme and alkaline hydrolysis methods, using vitamin standards, individual vitamin tablets and multivitamin preparations. The amounts obtained from the analysis were compared with the declared values. Recovery studies were also carried out. The method of acid hydrolysis with 0.1N sulphuric acid was found suitable for use and was thus adopted as the extraction procedure for the analysis of 10 multivitamin preparations obtained from various pharmaceutical outlets. For most of these preparations, the amount obtained were close to the declared values, except for folic acid and cyanocobalamin. Further trials on folic acid showed that the problem could be resolved by omitting the filtration step in the final extract after acid hydrolysis and diluting with 0.01N sodium hydroxide before processing for chromatography. Vitamin B12 was not detectable using the present chromatography system probably because of its low concentration in the samples studied.


[Latent sources of contact allergy].
In individuals sensitized to many contact allergens in the course of 4th immunological mechanism, in whom allergic contact dermatitis develops at the site of exposure to haptens, disseminated eczematous skin lesions might be provoked by latent source of hapten, which penetrates to the body omitting the skin. The most frequent clinical situations include: allergy to drugs, food additives, inhaled chemicals originated from plants, allergic reactions to metal endoprostheses used in orthopaedics and/or dentistry, and all conditions facilitating penetration of hapten directly to the blood through damaged skin (erosions, ulcers, etc.) and/or under occlusive dressings.


INCIPIENT SPECIATION BY SEXUAL ISOLATION IN DROSOPHILA MELANOGASTER: VARIATION IN MATING PREFERENCE AND CORRELATION BETWEEN SEXES.
Genetic divergence for characters pertaining to reproductive isolation is of considerable interest in evolutionary biology. Since most studies concentrate on sibling species (for recent reviews, see Wu et al. 1996), we would like to know how much genetic variation exists between populations that are at an incipient stage of speciation. To answer this question, we have begun measuring variations in mating preference among natural isolates of Drosophila melanogaster, represented by the cosmopolitan and Zimbabwe sexual races. We quantify the variation in mating preference and success in both sexes by using a multiple-choice design and an index that is suited to cases of strong asymmetry in mate choice. Different designs and indices for measuring sexual isolation are also discussed. These sexual traits are entirely genetically determined. Surveying four populations in southern Africa and additional cosmopolitan lines, we observe extensive genetic variation in sexual characters as well as strong correlation between sexes. The populations are highly differentiated and represent various stages of evolution between the African and the cosmopolitan type of sexual behaviors. The genetic variation and correlation for these sexual characters coupled with their geographical pattern have interesting implications for models of speciation by sexual selection.


Experience and Management of Intravascular Injection with Facial Fillers: Results of a Multinational Survey of Experienced Injectors.
Intravascular injection leading to skin necrosis or blindness is the most serious complication of facial injection with fillers. It may be underreported and the outcome of cases are unclear. Early recognitions of the symptoms and signs may facilitate prompt treatment if it does occur avoiding the potential sequelae of intravascular injection. To determine the frequency of intravascular injection among experienced injectors, the outcomes of these intravascular events, and the management strategies. An internet-based survey was sent to 127 injectors worldwide who act as trainers for dermal fillers globally. Of the 52 respondents from 16 countries, 71 % had ≥11 years of injection experience, and 62 % reported one or more intravascular injections. The most frequent initial signs were minor livedo (63 % of cases), pallor (41 %), and symptoms of pain (37 %). Mildness/absence of pain was a feature of 47 % of events. Hyaluronidase (5 to >500 U) was used immediately on diagnosis to treat 86 % of cases. The most commonly affected areas were the nasolabial fold and nose (39 % each). Of all the cases, only 7 % suffered moderate scarring requiring surface treatments. Uneventful healing was the usual outcome, with 86 % being resolved within 14 days. Intravascular injection with fillers can occur even at the hands of experienced injectors. It may not be always associated with immediate pain or other classical symptoms and signs. Prompt effective management leads to favorable outcomes, and will prevent catastrophic consequences such as skin necrosis. Intravascular injection leading to blindness may not be salvageable and needs further study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Neuropeptide Y-Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis.
Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroendocrine signal neuropeptide Y (NPY) mediated brain-gut-bone axis has come to light. Herein, it is reported that exogenous overexpression of NPY reduced bone formation, damaged bone microstructure, and up-regulated the expressions of pyroptosis-related proteins in subchondral cancellous bone in ovariectomized (OVX) rats, but Y1 receptor antagonist (Y1Ra) reversed these changes. In addition, it is found that exogenous overexpression of NPY aggravated colonic inflammation, impaired intestinal barrier integrity, enhanced intestinal permeability, and increased serum lipopolysaccharide (LPS) in OVX rats, and Y1Ra also reversed these changes. Most importantly, NPY and Y1Ra modulated the microbial diversity and changed the community composition of GM in OVX rats, and thereby affecting the metabolites of GM (e.g., LPS) entering the blood circulation. Moreover, fecal microbiota transplantation further testified the effect of NPY-mediated GM changes on bone. In vitro, LPS induced pyroptosis, reduced viability, and inhibited differentiation of osteoblasts. The study demonstrated the existence of NPY-mediated brain-gut-bone axis and it might be a novel emerging target to treat PMO.


Characteristics of localized surface plasmon resonance of nanostructured Au patterns for biosensing.
Periodic arrays of pseudotetrahedal-shaped gold nanoparticles were fabricated using nanosphere lithography (NSL) and examined for localized surface plasmon resonance (LSPR). The dependence of the LSPR on particle size of the periodic gold nanostructures was explored for potential application as a new biosensor. With increasing size and height of the Au nanoparticles, the absorption peak of the LSPR shifts to the longer wavelength and becomes relatively sharper. With thinner metal deposition or finer Au nanostructure, the absorption signal varies more sensitively for the changes in the Au particle size. The binding affinity study for biotin-streptavidine system on the Au nanopat-terns resulted in blue-shifted absorption signal, opening up the possibility of the nanostructured Au pattern as a new LSPR biosensor.


Accessory navicular syndrome as a cause of foot pain during stroke rehabilitation.
Although usually asymptomatic, an accessory navicular bone can lead to medial foot pain, especially in younger people engaged in high impact sports. In many such cases, the tendon of posterior tibialis (which inverts and plantarflexes the foot) inserts onto the accessory bone resulting in greater strain on the tendon. In the present case, pain due to an accessory navicular bone first developed during stroke rehabilitation in a 69-year-old man. The relative overactivity of posterior tibialis in strokes involving the leg and overuse due to active rehabilitation were likely contributors. An accessory navicular syndrome should be considered as a cause of medial foot pain in patients following a stroke. As in our case, conservative management with rest, ice and elevation is usually successful.


Transplant center regulations--a mixed blessing? An ASTS Council viewpoint.
The Centers for Medicare and Medicaid Services (CMS) has developed a set of regulations that spell out the Conditions of Participation (CoPs) for provider hospitals that wish to be certified (and thus eligible for reimbursement) by Medicare for transplant services. The American Society of Transplant Surgeons (ASTS) Council has played a major role in providing CMS with advice and guidance in the development and ongoing implementation of these conditions through a process of fruitful dialogue. In this report, we highlight the events that led to the development of the regulations and describe the process to date in implementing the CoPs. We have raised some important questions regarding the effectiveness of the regulations for improving safety, and we have highlighted the cost associated with their implementation. This report has been vetted by and represents the opinions of the Council of the ASTS.


Nailfold capillaroscopy and laser Doppler flowmetry during standardised cold challenge to evaluate capillary pattern and digital flow in idiopathic acrocyanosis.
Quantitative correlation between capillary morphologic patterns and digital pulp flow in idiopathic acrocyanosis (IA) is as yet unexplained. We studied capillary pattern, scored according mainly to capillary dilatation and tortuosity. Digital flow was recorded by laser Doppler flowmetry during a standardised cooling and rewarming thermal challenge in a controlled thermostatic chamber. A negative correlation was found by linear regression analysis between increasing capillary abnormalities and decreasing flow rates both at rest and during cooling, while a positive correlation was observed among the presence and intensity of the flow stop reaction during cold challenge and the decrease of hyperaemic re-flow in the rewarming phase. Further investigations may be justified to assess the nature of these abnormalities, whether constitutional or induced by prolonged cold exposure. For this purpose, a standardised method, as the cooling-rewarming challenge, could verify the several pathophysiological hypotheses proposed for vascular acrosyndromes. We need to use a subjective method such as capillaroscopy-based scoring (as in our study endorsed by an objective technique) to acquire the necessary reliability and reproducibility in the functional diagnosis. In fact IA patients with lower morphologic scores show better flow properties.


Treatment of hepatitis C virus infection: updated Swedish Guidelines 2016.
In a recent expert meeting, Swedish recommendations for the treatment of hepatitis C virus (HCV) infection were updated. An interferon-free combination of direct-acting antiviral agents is considered and indicated for all patients with chronic HCV infection, but the ability to treat all is limited primarily by high cost of medication. The group of patients prioritized for therapeutic intervention has been extended to also include fertile women desiring to become pregnant. A more thorough discussion of treatment for people who inject drugs (PWIDs) in order to diminish transmission is included, and the clinical significance of baseline NS5A resistance associated variants (RAVs), also known as resistance associated substitutions (RASs), for the treatment of HCV genotype 1a or 3 infection is discussed.


Co-existence of primary biliary cirrhosis and primary sclerosing cholangitis: a rare overlap syndrome put in perspective.
Overlap syndromes between autoimmune hepatitis and both primary biliary cirrhosis and primary sclerosing cholangitis are well described, but overlap between primary biliary cirrhosis and primary sclerosing cholangitis is not recognized. We present two cases of an unusual autoimmune liver disease, both of which included an overlap between primary biliary cirrhosis and primary sclerosing cholangitis, while one had features of all three conditions. The diagnoses were based on clinical, biochemical, serological, histological and cholangiographic findings. The two cases were identified from a consecutive cohort of 261 patients with autoimmune liver disease followed prospectively in secondary care over a 20-year period, which gives perspective to this uncommon overlap syndrome.


Studies on hemagglutination test on filariasis. I. The fractionation and purification of antigens by column chromatography and disc electrophoresis.
The fractionation of antigens for hemagglutination test from adult worms of Dirofilaria (D.) immitis was carried out by defatting with diethylether, sonication, centrifugation, gel-filtration on sephadex G-100 column, DEAE cellulose column chromatography, saturation with ammonium sulfate and disc electrophoresis. An antigen FPSD4 thus obtained, showed potent HA activity against sera from patients infected with Wuchereria (W.) bancrofti. But it was also reactive with normal sera. After elimination of the cross-reacting substance from antigen FPSD4 by the saturation of ammonium sulfate, a specific antigen FPSD4-2 was obtained. By the tests using FSCD4-2 in a protein concentration of 20 mug/ml, sera of 27 patients with microfilariae of W. bancrofti in their blood were examined and 18 positive cases (66.7% positive) were obtained. With 21 normal human sera, no cross reaction was found. As antigen FPSD4-2 showed about 20 protein bands, the further purification of the antigen by disc electrophoresis was carried out. Among three subfractions thus obtained, FPSDA which contained 5 protein bands was most reactive and specific.


The skin microbiome of cow-nose rays (Rhinoptera bonasus) in an aquarium touch-tank exhibit.
Public aquaria offer numerous educational opportunities for visitors while touch-tank exhibits offer guests the ability to directly interact with marine life via physical contact. Despite the popularity of touch-tanks, there is a paucity of research about animal health in these exhibits and, in particular, there is little research on the microbial communities in these highly interactive exhibits. Microbial community structure can have implications for both host health and habitat function. To better understand the microbiome of a touch-tank we used high-throughput sequencing of the 16S rRNA gene to analyze the microbial community on the dorsal and ventral surfaces of cow-nose rays (Rhinoptera bonasus) as well as their environment in a frequently visited touch-tank exhibit at the New England Aquarium. Our analyses revealed a distinct microbial community associated with the skin of the ray that had lower diversity than the surrounding habitat. The ray skin was dominated by three orders: Burkholderiales (∼55%), Flavobacteriales (∼19%), and Pseudomonadales (∼12%), taxonomic groups commonly associated with other fish species. Our results provide a survey of ray-associated bacterial communities in a touch-tank environment, thereby laying the foundation for future studies examining the role of potential challenges to ray microbiota and their associated health.


[Acute pancreatitis in children].
Acute pancreatitis is probably commoner in children than was previously thought. In children it is most commonly associated with trauma or viral infection. The presentation may be subtler than in adults, requiring a high index of suspicion in the clinician. In three children, two boys aged 4 and 10 and a girl of 15 years, acute pancreatitis was suspected because of the findings at ultrasonography and endoscopic retrograde cholangiopancreatography performed when the disease recurred (the boy aged 4), apathy and immobility without dehydration or other obvious causes (the boy aged 10), and severe abdominal pain in combination with vomiting (the girl). All three patients had severely increased (urinary) amylase levels. Most often, acute pancreatitis in children tends to be a self-limiting disease which responds well to conservative treatment.


Poor bladder compliance due to malacoplakia with xanthogranulomatous cystitis: A case report.
Either malacoplakia or xanthogranulomatous cystitis (XC) is a rare chronic infection disease of urinary bladder, which often mimics bladder masses undifferentiated from malignance and results in severe lower urinary tract symptoms. The malacoplakia combined with XC is even rarer in the literature. A 64-year-old female, who presented with nocturia, frequency of micturition, severe urgency with occasional urinary incontinence, and recurrent hematuria for >2 years, was diagnosed with azotemia and anemia. In addition, two 1.0 × 1.0 cm masses of bladder were detected by computer tomography. Malacoplakia combined with xanthogranulomas cystitis was diagnosed histologically. Video urodynamic test showed poor bladder compliance (9 mL/comH2O), markedly decreased maximum bladder capacity (120 mL), and right vesicoureteral reflux at a low intravesical pressure level (25 cmH2O). Transurethral resection of bladder masses was carried out after treatment of urinary infection by intravenous piperacillin-tazobactam. Oral Ciprofloxacin and Tolterodine were postoperatively used to prevent recurrent lower urinary tract infections and alleviate detrusor overactivity. The treatment did not alleviate azotemia, frequency, urgency with incontinence, and bilateral hydroureteronephrosis, but the patient refused to undergo bladder augmentation on account of her poor economic status. Malacoplakia or/and xanthogranulomas cystitis may lead to poor bladder compliance and video urodynamic study should be considered in patients with refractory chronic lower urinary tract symptoms.


[Does the intensity of acid gastroesophageal reflux influence chosen parameters of physical development in children and youth?].
THE AIM OF THE STUDY was to analyse physical development of children and youth with gastroesophageal reflux disease. one hundred thirteen patients between 2 and 18 years of age, with gastroesophageal reflux disease were included in the study. Height and weight were also analysed using the percentile chart of Warsaw children from 1999. Patients were divided into three groups according to the intensity of gastroesophageal reflux in 24-hours pH-metry: group I: minimal degree of gastroesophageal reflux - 3,4-9,9% total time (n=52), group II: moderate degree of gastroesophageal reflux - 10-19,9% total time (n=39), group III: significant degree of gastroesophageal reflux > 20% total time (n=22). in group I, weight less than 3 percentile was found in 1,9% patients, height in 5,76%, weight between 3 and 10 percentile in 11,53%, height in 3,80%, weight between 90-97 percentile in 3,80%, height in 15,38% and weight above 97 percentile in 11,53%, height in 15,38%. In group II weight less than 3 percentile was found in 2,56% patients, height less than 3 percentile was not observed, weight between 3 and 10 percentile in 11,53%, height in 2,56%, weight above 97 percentile in 7,69%, height in 12,82% and weight between 90-97 percentile in 5,12%, height in 10,24%. In group III, weight and height less than 3 percentile was found in 13,63%, weight between 3 and 10 percentile in 13,63%, height in 4,54%, weight above 97 percentile in 4,54%, height in 13,63%, weight between 90-97 percentile in 18,18%, height in 22,72%. no statistically significant correlations between the intensity of gastroesophageal reflux and the weight and height in children and youth were found.


Revisiting the Wald Test in Small Case-Control Studies With a Skewed Covariate.
The Wald test is routinely used in case-control studies to test for association between a covariate and disease. However, when the evidence for association is high, the Wald test tends to inflate small P values as a result of the Hauck-Donner effect (HDE). Here, we investigate the HDE in the context of genetic burden, both with and without additional covariates. First, we examine the burden-based P values in the absence of association using whole-exome sequence data from 1000 Genomes Project reference samples (n = 54) and selected preterm infants with neonatal complications (n = 74). Our careful analysis of the burden-based P values shows that the HDE is present and that the cause of the HDE in this setting is likely a natural extension of the well-known cause of the HDE in 2 × 2 contingency tables. Second, in a reanalysis of real data, we find that the permutation test provides increased power over the Wald, Firth, and likelihood ratio tests, which agrees with our intuition since the permutation test is valid for any sample size and since it does not suffer from the HDE. Therefore, we propose a powerful and computationally efficient permutation-based approach for the analysis and reanalysis of small case-control association studies.


[The neurochemical basis of recurrent inhibition in the reflex arch of the defensive reaction].
Mechanisms of habituation in the network of identified neurones were investigated in isolated preparation of central nervous system in the snail Helix. It has been found that intracellularly induced spike discharge in premotor command neurones decreases synaptic responses to repeated nerve stimulation in all recorded command neurones. Application of the neuropeptide FMRFamide elicits similar changes in the network. Taking into account that the investigated command neurones contain FMRFamide, as was shown immunochemically, it is possible to assume the existence of recurrent inhibition in the network underlying avoidance reactions. This recurrent inhibition causes habituation of the network output in the cases when the repeated stimuli do not evoke sensitization via activation of serotonergic cells.


Recombinant transthyretin purification and competitive binding with organohalogen compounds in two gull species (Larus argentatus and Larus hyperboreus).
Glaucous gulls (Larus hyperboreus) from Svalbard, Norway (marine), and herring gulls (Larus argentatus) from the Laurentian Great Lakes (freshwater) of North America are differentially exposed to persistent and bioaccumulative anthropogenic contaminants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ether (PBDE) flame retardants and metabolic products. Such compounds can potentially perturb hormone transport via binding interactions with proteins such as transthyretin (TTR, prealbumin). In this present study, we isolated, cloned and sequenced TTR cDNA from the brain and liver of two species (herring and glaucous gull), which, to our knowledge, is the first report describing the TTR nucleic acid and amino acid sequences from any gull species. Identical TTR nucleotide and amino acid sequences were obtained from both gull species (liver and brain). Recombinant TTR (rTTR) was expressed and purified, and determined as a monomer of 18 kDa and homodimer of 36 kDa that putatively is comprised of the two protein monomers. Concentration dependent, competitive TTR-binding curves with each of the natural TTR ligands 3,5,3'-triiodothyronine (T(3)) and thyroxine (T(4)) were generated as well as by treatment with a range of concentrations (10(-3)-10(5)nM) of 2,2',3,4',5,5',6-heptaCB (CB187), 2,2',4,4'-tetrabromoDE (BDE47), and hydroxyl- (OH) and methoxyl (MeO)-containing analogs (i.e., 4-OH-CB187, 6-OH-BDE47, 4'-OH-BDE49, 4-MeO-CB187, and 6-MeO-BDE47). Relative to the nonsubstituted BDE47 and CB187 and their MeO-substituted analogs, the OH-substituted analogs all had lower K(i) and K(d) values, indicating greater affinity and more potent competitive binding to both T(3) and T(4). The OH-substitution position and/or the diphenyl ether substitution of the four bromine atoms resulted in more potent, greater affinity, and greater relative potency for 4'-OH-BDE49 relative to 6-OH-BDE47. CB187 was more comparable in binding potency and affinity to 4-OH-CB187, then was 6-OH-BDE47 and 4'-OH-BDE49 relative to BDE47 where the binding potency and affinity was several orders of magnitude greater for 6-OH-BDE47 and 4'-OH-BDE49. This indicated that the combination of the more thyroid hormone-like brominated diphenyl ether backbone (relative to the chlorinated biphenyl backbone), and in combination of having an OH-group, results in a more effective competitive ligand on gull TTR relative to both T(3) and T(4). Known circulating levels of 4-OH-CB187, 6-OH-BDE47, and 4'-OH-BDE49 in the plasma of free-ranging Svalbard glaucous gulls were comparable to the concentration of in vitro competitive potency of T(3) and T(4) with gull TTR. These results suggest that environmentally relevant and selected OH-containing PCB, and to a lesser extent PBDE congeners have the potential to be physiologically effective in these gull species via perturbation of T(4) and T(3) transport.


Helichrysum araxinum Takht. ex Kirp. grown in Italy: volatiloma composition and in vitro antimicrobial activity.
In the present work the composition of biogenic volatile organic compounds (BVOCs) and the essential oil (EO) of Helichrysum araxinum Takht. ex Kirp. aerial parts, together with the antimicrobial activity, were investigated. The results showed the prevalence of sesquiterpene hydrocarbons in both spontaneous emissions as well as in the EO. The main compounds of BVOCs were γ-curcumene (10.7%), γ-muurolene (9.2%), and β-selinene (8.5%). This latter constituent also showed a similar amount in the EO and represented the most abundant compounds together with α-selinene (8.0%). It is Interesting to note the same percentage of monoterpene hydrocarbons (MHs) in both the aroma profile and the EO (18.0%) with the same most abundant compounds: β-pinene (6.3% in BVOCs vs. 5.1% in EO, respectively) and limonene (4.5% in VOCs vs. 4.9% in EO, respectively). With regard to the antimycotic activity, the EO showed to be inactive against the tested strains, while a moderate antibacterial activity was shown against Staphylococcus isolates.


Real versus artifactual symmetry-breaking effects in Hartree-Fock, density-functional, and coupled-cluster methods.
We have examined the relative abilities of Hartree-Fock, density-functional theory (DFT), and coupled-cluster theory in describing second-order (pseudo) Jahn-Teller (SOJT) effects, perhaps the most commonly encountered form of symmetry breaking in polyatomic molecules. As test cases, we have considered two prototypical systems: the 2Sigmau+ states of D( infinity h) BNB and C3+ for which interaction with a low-lying 2Sigmag+ excited state leads to symmetry breaking of the nuclear framework. We find that the Hartree-Fock and B3LYP methods correctly reproduce the pole structure of quadratic force constants expected from exact SOJT theory, but that both methods appear to underestimate the strength of the coupling between the electronic states. Although the Tamm-Dancoff (CIS) approximation gives excitation energies with no relationship to the SOJT interaction, the random-phase-approximation (RPA) approach to Hartree-Fock and time-dependent DFT excitation energies predicts state crossings coinciding nearly perfectly with the positions of the force constant poles. On the other hand, the RPA excited-state energies exhibit unphysical curvature near their crossings with the ground (reference) state, a problem arising directly from the mathematical structure of the RPA equations. Coupled-cluster methods appear to accurately predict the strength of the SOJT interactions between the 2Sigmau+ and 2Sigmag+ states, assuming that the inclusion of full triple excitations provides a suitable approximation to the exact wave function, and are the only methods examined here which predict symmetry breaking in BNB. However, coupled-cluster methods are plagued by artifactual force constant poles arising from the response of the underlying reference molecular orbitals to the geometric perturbation. Furthermore, the structure of the "true" SOJT force constant poles predicted by coupled-cluster methods, although correctly positioned, has the wrong structure.


CCR3 is required for tissue eosinophilia and larval cytotoxicity after infection with Trichinella spiralis.
The CCR3 binds at least seven different CC chemokines and is expressed on eosinophils, mast cells (MC), and a subset of Th cells (Th2) that generate cytokines implicated in mucosal immune responses. Using mice with a targeted disruption of CCR3 (CCR3(-/-)) and their +/+ littermates, we investigated the role of CCR3 in the amplification of tissue eosinophilia and MC hyperplasia in the mouse after infection with Trichinella spiralis. In CCR3(-/-) mice, eosinophils are not recruited to the jejunal mucosa after infection and are not present in the skeletal muscle adjacent to encysting larvae. In addition, the number of cysts in the skeletal muscle is increased and the frequency of encysted larvae exhibiting necrosis is reduced. The CCR3(-/-) mice exhibit the expected MC hyperplasia in the jejunum and caecum and reject the adult worms from the small intestine at a normal rate. This study is consistent with distinct functions for MC (adult worm expulsion) and eosinophils (toxicity to larvae) in immunity to a helminth, T. spiralis, and defines the essential requirement for CCR3 in eosinophil, but not MC recruitment to tissues.


[Pseudarthrosis of the capitate bone. Report of 2 cases].
Well protected by its central position and richly vascularized, the capitate bone is rarely involved in posttraumatic pseudarthrosis. Drawing on two cases, the present study will describe anatomy, aetiology, pathogenesis, diagnosis, and therapy of pseudarthroses of the capitate. Restoration of the physiological capitate height was achieved in both cases with a corticocancellous bone graft from the iliac crest which led on to bony union within three months.


Nonpyramidal neurons in the primate basolateral amygdala: A Golgi study in the baboon (Papio cynocephalus) and long-tailed macaque (Macaca fascicularis).
Nonpyramidal GABAergic interneurons in the basolateral nuclear complex (BNC) of the amygdala are critical for the regulation of emotion. Remarkably, there have been no Golgi studies of these neurons in nonhuman primates. Therefore, in the present study we investigated the morphology of nonpyramidal neurons (NPNs) in the BNC of the baboon and monkey using the Golgi technique. NPNs were scattered throughout all nuclei of the BNC and had aspiny or spine-sparse dendrites. NPNs were morphologically heterogeneous and could be divided into small, medium, large, and giant types based on the size of their somata. NPNs could be further divided on the basis of their somatodendritic morphology into four types: multipolar, bitufted, bipolar, and irregular. NPN axons, when stained, formed dense local arborizations that overlapped their dendritic fields to varying extents. These axons always exhibited varying numbers of varicosities representing axon terminals. Three specialized NPN subtypes were recognized because of their unique anatomical features: axo-axonic cells, neurogliaform cells, and giant cells. The axons of axo-axonic cells formed "axonal cartridges," with clustered varicosities that contacted the axon initial segments of pyramidal neurons (PNs). Neurogliaform cells had small somata and numerous short dendrites that formed a dense dendritic arborization; they also exhibited a very dense axonal arborization that overlapped the dendritic field. Giant cells had very large irregular somata and long, thick dendrites; their distal dendrites often branched extensively and had long appendages. In general, the NPNs of the baboon and monkey BNC, including the specialized subtypes, were similar to those of rodents.


A multidisciplinary study of onchocerciasis in Bure area, Ethiopia.
A clinicoepidemiological and entomological study of onchocerciasis was conducted in Bure area, Illubabor Administrative Region, in October 1987. All 1063 houses in four villages were numbered and census taken. The total population was 4119. Of the total 1063 houses, 107 (10.07%) were selected by systematic random sampling and all members of these households were examined. History, physical examination, and skin biopsy were taken. Of 4119 people in the area, 3555 (86.3%) were indigenous and 564 (13.7%) settlers. Four hundred and three of the former and 68 of the latter were studied. Clinical manifestations were mild and ocular onchocerciasis was not encountered. One hundred and sixteen (24.6%) had O. volvulus in the skin; with a mean of 11.7 microfilariae per milligram of skin. Positivity in males was 1 1/2 times that in females. None of the settlers had positive skin snips. We concluded that onchocerciasis is hypoendemic in Bure area with mild clinical manifestations. Adult and aquatic stages of Simulium were collected for later identification, and a preliminary report indicates that S. damnosum s.l. is the most likely vector.


Genetic relationship among isolates of Helicobacter pylori: evidence for the existence of a Helicobacter pylori species-complex.
We investigated the population genetics of 23 isolates of H. pylori by allozyme electrophoresis using 16 enzyme loci. Isolates were obtained from adult patients of whom 48% were of Greek extraction. Eight patients (35%) had an active duodenal ulcer. Allelic variation per loci ranged from 2 to 11 alleles. Four major genetic clusters were apparent, having > 75% fixed genetic differences. There was no distinct clustering (clonal structure) on the basis of the geographical origin of the persons from whom isolates were obtained, indicating that this bacterium has not recently jumped a species barrier into humans. Isolates associated with ulcer disease were not monophyletic, with isolates from ulcer patients being found in phylogenetically diverse branches of the dendogram derived from the data. Based on the genetic diversity of H. pylori isolates, we propose that isolates should be classified as belonging not to a single species but to a 'Helicobacter pylori species-complex'.


Coordinated movement is influenced by prenatal light experience in bobwhite quail chicks (Colinus virginianus).
Sensory-motor development begins early during embryogenesis and is influenced by sensory experience. Little is known about the prenatal factors that influence the development of motor coordination. Here we investigated whether and to what extent prenatal light experience can influence the development of motor coordination in bobwhite quail hatchlings. Quail embryos were incubated under four light conditions: no light (dark), 2h of total light (2HR), 6h of total light (6HR), and diffused sunlight (controls). Hatchlings were video recording walking down a runway at three developmental ages (12, 24, and 48h). Videos were assessed for forward locomotion, a measurement of motor coordination, falls, a measurement of motor instability, and motivation to complete the task. We anticipated a linear decline of coordination with a reduction in prenatal light experience and improved coordination with age. Furthermore, as motor coordination becomes more laborious we anticipated motivation to complete the task would decline. However, our findings revealed hatchlings did not uniformly improve with age as expected, nor did the reduction of light result in a linear reduction in motor coordination. Instead, we found a more complex relationship with 6HR and 2HR hatchlings showing distinct patterns of stability and instability. Similarly, we found a reduction in motivation within the 6HR light condition. It appears that prenatal light exposure influences the development of postnatal motor coordination and we discuss these finding in light of neurodevelopmental processes influenced by light experience.


The incremental impact of cardiac MRI on clinical decision-making.
Despite a significant expansion in the use of cardiac MRI (CMR), there is inadequate evaluation of its incremental impact on clinical decision-making over and above other well-established modalities. We sought to determine the incremental utility of CMR in routine practice. 629 consecutive CMR studies referred by 44 clinicians from 9 institutions were evaluated. Pre-defined algorithms were used to determine the incremental influence on diagnostic thinking, influence on clinical management and thus the overall clinical utility. Studies were also subdivided and evaluated according to the indication for CMR. CMR provided incremental information to the clinician in 85% of cases, with incremental influence on diagnostic thinking in 85% of cases and incremental impact on management in 42% of cases. The overall incremental utility of CMR exceeded 90% in 7 out of the 13 indications, whereas in settings such as the evaluation of unexplained ventricular arrhythmia or mild left ventricular systolic dysfunction, this was <50%. CMR was frequently able to inform and influence decision-making in routine clinical practice, even with analyses that accepted only incremental clinical information and excluded a redundant duplication of imaging. Significant variations in yield were noted according to the indication for CMR. These data support a wider integration of CMR services into cardiac imaging departments. These data are the first to objectively evaluate the incremental value of a UK CMR service in clinical decision-making. Such data are essential when seeking justification for a CMR service.


Maximizing Mobilization of Resources for Unplanned Certified Registered Nurse Anesthetist Staffing Deficiencies in a Large Midwest Multi-Hospital Trauma Center.
Acute staffing deficiencies pose a challenge for hospitals because shortages can negatively impact patient safety. The purpose of this study was to examine the most effective staff recall system (SRS) for Certified Registered Nurse Anesthetists (CRNAs) during times of acute staffing deficiencies, whether from unforeseen emergencies or mass call outs. A preposttest design was used to explore the efficacy of the hospital's current CRNA SRS compared to a newly developed short message system (SMS) Acute Staffing Deficiency Recall Plan. Two 60-minute simulation drills were conducted to test the two systems with a convenience sample of 317 CRNAs. Data were gathered related to CRNAs: contacted, availability, and length of time to contact. Surveys were utilized pre/ post to evaluate knowledge, confidence, and selfefficacy regarding the recall systems. During the first simulation drill, 26% of CRNAs were contacted and 19% confirmed availability within 60 minutes using the standard CRNA SRS. During the second simulation, 86% of the CRNAs were contacted and 38% confirmed availability using the SMS messaging system within 60 minutes (P < .00001 and P < .0001 respectively). The SMS messaging improved CRNA contact by 60% and availability improved by 19% over the standard SRS.


Two-dimensional gel electrophoresis of sheep plasma proteins: genetic polymorphism of an alphal-protease inhibitor and a post-transferrin.
Two-dimensional electrophoretic analysis of sheep plasma proteins was performed by a first-dimension separation in agarose gel (pH 5.0) followed by a second-dimension one in horizontal polyacrylamide gel (pH 9.0). This method resulted in improved and reproducible separation of many alpha- and beta-globulins. Two groups of alpha 1-globulins, designated Pi-1 and Pi-2, were found to be protease inhibitors. These two inhibitors differed from each other in protease inhibitory spectra. Genetic polymorphism was observed for the Pi-2 protein and another unidentified protein, tentatively designated as post-transferrin (Ptf). Family data supported the hypothesis that Pi-2 and Ptf types were controlled by codominant, autosomal alleles. Three Pi-2 alleles and two Ptf alleles were observed in one population of the Gotland breed of sheep. The analysis of data from 50 informative matings showed no evidence of genetic linkage between the Pi-2, Ptf and transferrin (Tf) loci in the population of sheep studied.


Clinical Epidemiology of Mineral Bone Disorder Markers in Prevalent Hemodialysis Patients in the Xinjiang Uyghur Autonomous Region in China.
We investigated the clinical epidemiology of mineral bone disorder markers in prevalent hemodialysis (HD) patients in Xinjiang, the largest province in China. Data were obtained from 59 hospitals. A total of 3725 patients tracked from January 1 to December 31, 2014, were enrolled. Serum calcium (Ca) levels, phosphorus (P) levels, and intact parathyroid hormone (iPTH) levels were analyzed. Serum Ca levels were lower compared to the International Dialysis Outcomes and Practice Patterns Study (DOPPS4) and the Chinese DOPPS. The hypercalcemia rate was similar to DOPPS4 and lower than in the Chinese DOPPS. Serum P levels were higher than in DOPPS4 and lower than those in the Chinese DOPPS. Hyperphosphatemia rates were higher than DOPPS4 and lower than Chinese DOPPS. Serum iPTH levels were higher than in DOPPS4 and the Chinese DOPPS. We demonstrated higher serum P and iPTH levels in Xinjiang HD patients than in the DOPPS4 and Chinese DOPPS. In contrast, serum Ca levels were lower than the other two studies. High hypocalcemia and hyperphosphatemia rates may suggest that HD services in Xinjiang are inadequate. A multidiscipline chronic kidney disease (CKD) care program needs to be established to improve chronic kidney disease-mineral and bone disorder (CKD-MBD) target achievement in Xinjiang.


New compounds: peptide derivatives of the antitumor agent N-phosphonoacetyl-L-aspartic acid.
Two peptide forms of the antitumor transition state analogue N-phosphonoacetyl-L-aspartic acid (N2-phosphonoacetyl-N4-glycylglycinamidoethyl-L-asparagine and N1-glycylglycinamidoethyl-N2-phosphonoacetyl-L-isoasparagine ) have been synthesized to obtain potential medicinal agents useful as prodrugs or in a lysosomotropic carrier approach. The bridging unit, ethylenediamine, used for synthetic purposes might be of general interest.


Polypoid amelanotic melanoma: a diagnostic challenge.
Melanoma is a highly aggressive cutaneous malignancy with considerable risk for metastasis. These malignant tumors are typically pigmented given that they arise from melanocytes capable of producing melanin. Amelanotic melanomas are a rare variant and there is often a delay in diagnosis owing to lack of pigmentation. Although there are various presentations of amelanotic melanoma, a solitary polypoid nodule is unusual and warrants further reporting. Herein, we present a patient with a 3-year history of a tender firm, skin-to-pink colored polypoid nodule. Excisional biopsy and work up showed an aggressive amelanotic melanoma with depth of 20mm and nodal metastasis consistent with stage IIIC disease. This case highlights the necessity of recognition and prompt management of this rare subtype of melanoma.


The origins of protein phosphorylation.
The reversible phosphorylation of proteins is central to the regulation of most aspects of cell function but, even after the first protein kinase was identified, the general significance of this discovery was slow to be appreciated. Here I review the discovery of protein phosphorylation and give a personal view of the key findings that have helped to shape the field as we know it today.


High output cardiac failure in a parturient with hereditary haemorrhagic telangiectasia.
Hereditary haemorrhagic telangiectasia is a genetic condition which results in arteriovenous malformations involving the skin, mucous membranes, lung, brain, gastrointestinal tract, liver and spinal canal. The shunting of blood through arteriovenous malformations, especially in the liver,; leads to maldistribution of cardiac output. In order to supply blood to vital organs, cardiac output is increased through vasodilation, elevated stroke volume and elevated heart rate. Pregnancy can worsen the effects of the arteriovenous malformations. We present the peripartum management of a woman with hereditary haemorrhagic telangiectasia predominantly involving the liver that resulted in high output cardiac failure during two consecutive pregnancies.


Severe hypertension in childhood due to prolonged skin application of a mineralocorticoid ointment.
We report the case of a 9-year-old boy suffering from exzematous dermatitis who was treated for 6 years with a daily dose of 100 mg of a dermatological ointment containing 9 alpha-fluoroprednisolone-21-acetate. At examination the patient's blood pressure was persistently 230/160 mm Hg and was considered essential in origin after secondary forms of arterial hypertension had been excluded. Treatment with nifedipine and labetalol lowered the blood pressure to 150/100 mm Hg. When we became aware of the dermatological treatment, we advised its discontinuance. In the subsequent 7 days, the blood pressure fell to hypotensive levels (75/40 mm Hg) and then became normal a few days after discontinuance of the antihypertensive therapy. This case suggests that prolonged use of topical steroids, commonly prescribed for skin diseases, may cause hypertension, especially in childhood.


Sleep disturbances among medical students: a global perspective.
Medical students carry a large academic load which could potentially contribute to poor sleep quality above and beyond that already experienced by modern society. In this global literature review of the medical students' sleep experience, we find that poor sleep is not only common among medical students, but its prevalence is also higher than in non-medical students and the general population. Several factors including medical students' attitudes, knowledge of sleep, and academic demands have been identified as causative factors, but other potential mechanisms are incompletely understood. A better understanding about the etiology of sleep problems in medical trainees is essential if we hope to improve the overall quality of medical students' lives, including their academic performance. Sleep self-awareness and general knowledge appear insufficient in many studied cohorts, so increasing education for students might be one beneficial intervention. We conclude that there is ample evidence for a high prevalence of the problem, and research in this area should now expand towards initiatives to improve general sleep education for medical students, identify students at risk, and target them with programs to improve sleep.


Adiponectin gene SNP 276G --> T, nutrient intakes, and cardiovascular disease risk in Korean type 2 DM patients.
Single nucleotide polymorphism (SNP) in adiponectin gene has been associated with insulin resistance, diabetes, and cardiovascular disease (CVD). This study was performed to investigate the association of SNP 276G-->T at adiponectin gene with CVD risk factors in Korean type 2 diabetes mellitus (DM) patients. The subjects were 351 type 2 DM patients visited a DM clinic in Seoul, and the patients with known CVD were excluded. The adiponectin SNP 276G-->T was analyzed and dietary intakes were assessed by a Food Frequency Questionnaire. The prevalence of G/G, G/T, and T/T genotype was 47.6%, 43.3%, and 9.1%, respectively. Male subjects with T/T genotype showed significantly lower level of adiponectin and HDL-cholesterol and significantly higher C-reactive protein (CRP) level compared to G/G and G/T genotypes. In G/G genotype, protein intake was negatively correlated to body weight, BMI, and waist circumference, and there were positive correlation between carbohydrate intake and BMI, waist-hip ratio, and ApoB/apoA-1 ratio in G/T genotype. However, in T/T genotype, there was no significant association between macronutrient intakes and anthropometric and hematological values. In conclusion, CVD risk would be high in type 2 DM patients with T/T genotype, and the association of macronutrient intakes with anthropometric and hematologic factors was different among the three adiponectin genotypes. These results may imply the need for different dietary management regime according to adiponectin genotype to lower CVD complications in Korean type 2 DM patients.


Rapid determination of theophylline in human plasma by high-pressure liquid chromatography.
A rapid, specific, high-pressure liquid chromatographic method for the determination of theophylline in plasma was developed. The procedure is fast enough (21 min from receipt of blood to reporting value) to be used for emergency determinations. The sensitivity, precision, and accuracy are sufficient for routine monitoring of therapeutic levels in patients. The assay is specific enough to be valid in the presence of caffeine and theobromine. Metabolites of theophylline as well as a number of drugs do not interfere with the assay.


Radioimmunoassay for the detection of IgG antibodies to herpes simplex virus and its use as a prognostic indicator of HSV excretion in transplant recipients.
We report the development of a solid-phase radioimmunoassay for the detection of IgG antibodies to herpes simplex virus (HSV), using a mouse monoclonal antibody specific for the Fc portion of human IgG as the radiolabelled detecting antibody. The binding ratio to test antigen at a single serum dilution, 1:100, correlated significantly with the endpoint titre by radioimmunoassay and with neutralising antibody titre. When compared to neutralisation the radioimmunoassay had a sensitivity of 100% and a specificity of 93%. We believe that the anomalous results are not false positives but represent an increased sensitivity of the radioimmunoassay. We found, by either radioimmunoassay or neutralisation, that high levels of antibody prior to transplantation were associated with a significantly increased risk of HSV excretion post-transplantation in both renal and bone marrow transplant recipients. Thus the radioimmunoassay is a sensitive, specific, and rapid test that can be used as a prognostic indicator of HSV excretion in transplant recipients.


Wait-and-see or radical surgery for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy: a cohort study.
A wait-and-see policy might be considered instead of surgery for rectal cancer patients with no residual tumor or involved lymph nodes on imaging or endoscopy after neoadjuvant chemoradiotherapy (clinical complete response, cCR). In this cohort study, we compared the oncologic outcomes of rectal cancer patients with a cCR who were managed according to a wait-and-see policy (observation group) or with surgery (surgery group). In the observation group, follow-up was performed every 3 months for the first year and consisted of MRI, endoscopy with biopsy, computed tomography and transrectal ultrasonography. In the surgery group, patients received radical surgery. Long-term oncologic outcomes were estimated using Kaplan-Meier curves. Thirty patients were enrolled in the observation group (median follow-up, 60 months; range, 18-100 months), and 92 patients were enrolled in the surgery group (median follow-up, 58 months; range, 18-109 months). The 5-year disease free survival and overall survival rates were similar in the two groups: 90.0% vs. 94.3% (P = 0.932) and 100.0% vs. 95.6% (P = 0.912), respectively. We conclude that for rectal cancer patients with a cCR after neoadjuvant chemoradiotherapy, a wait-and-see policy with strict selection criteria, follow-up and salvage treatments achieves outcomes at least as good as radical surgery. Additionally, we declare that the pCR (pathologic complete regression) and non-pCR subgroups of patients with a cCR have similar long-term failure (local recurrence and/or distant metastasis) rate.


[Clinical manifestations and acute myocardial infarction in women treated with primary coronary angioplasty].
The differences in presentation, complications, and outcome of acute myocardial infarction treated with primary coronary angioplasty were compared in male and female patients. Consecutive patients with acute myocardial infarction who were admitted within 12 hr of onset underwent primary percutaneous coronary intervention, including 120 female (31%) and 264 male (69%) patients. There were significantly more patients with diabetes mellitus (42% vs 31%, p = 0.03), and hyperlipidemia(56% vs 38%, p = 0.001), and fewer patients with current smoking (10% vs 60%, p < 0.0001) in the female group than in the male group (p < 0.01). The female group was significantly older (75 +/- 11 vs 67 +/- 12 years, p < 0.0001). The value of acute phase brain natriuretic peptide was significantly higher (483 +/- 543 vs 306 +/- 404 pg/ml, p = 0.001), and peak creatine kinase value was significantly lower (1,743 +/- 1,732 vs 2,855 +/- 2,997 IU/l, p = 0.0003) in the female group than in the male group. Both Killip's classification on admission (p = 0.04) and Thrombolysis in Myocardial Infarction grade soon after mechanical reperfusion therapy (p = 0.03) were significantly worse in the female group. There were significantly more patients with heart failure in the female group (40% vs 27%, p = 0.04). The cardiac mortality rates during 6 months was significantly higher in the female group (11% vs 5%, p = 0.02). However, multivariate analysis showed that female sex was not an independent predictor of cardiac death. Female patients with acute myocardial infarction seemed to have a poor prognosis, in spite of lower peak creatine kinase value and higher brain natriuretic peptide value. The reasons for poorer outcomes in women were considered to be patient background, such as higher age and diabetes mellitus, and condition of heart failure on admission.


Responses to an in-basket activity: the role of work stress, behavioral control, and informational control.
This study was undertaken to examine the main and interactive effects of work stress and work control on levels of adjustment. Work stress, behavioral control, and informational control were manipulated in an experimental setting in which participants (N = 192) completed an in-basket activity. Although minimal support was found for the main and interactive effects of objective work stress, behavioral control, and informational control on adjustment, analyses involving the subjective measures of these variables revealed strong support for the proposal that work stress, behavioral control, and informational control would exert main effects on adjustment. There was also evidence that subjective levels of behavioral control buffered the negative effects of subjective work stress on positive mood, subjective task performance, and task satisfaction.


Women's representation in clinical trials of patients with chronic kidney disease.
Sex and gender differences in chronic kidney disease (CKD), including epidemiology and response to treatment, remain poorly understood. This study aimed to investigate how women are represented in CKD clinical trials and whether sex- and gender-disaggregated outcomes were reported. Clinical trials on CKD were identified from ClinicalTrials.gov. Randomised, phase 3/4 trials with ≥100 participants were selected to quantify women's representation among participants by computing the participation:prevalence ratio (PPR) and investigating whether sex-disaggregated analyses had been performed. In total, 192 CKD trials registered on ClinicalTrials.gov and published between 1995 and 2022 were included. Overall, women accounted for 66 875 (45%) of the 147 136 participants. Women's participation in clinical trials was lower than their representation in the underlying CKD population globally (55%). The PPR was 0.75 (95% confidence interval 0.72-0.78), with no significant variation irrespective of mean age, CKD stage, dialysis, location, type of intervention or funding agency. A total of 39 (20%) trials reported sex-disaggregated efficacy outcomes and none reported sex-disaggregated safety outcomes. Women's participation in CKD clinical trials was lower than their representation in the underlying CKD population. Sex-disaggregated efficacy and safety outcomes were rarely reported. Improving women's enrolment into clinical trials is crucial to enable sex- and gender-disaggregated analysis and thus identify potential differences in treatment response between women and men.


Ex vivo fucosylation of third-party human regulatory T cells enhances anti-graft-versus-host disease potency in vivo.
Adoptive therapy with regulatory T cells (Tregs) to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation. We hypothesized that adding fucose to human Tregs, forming the Sialyl Lewis X moiety on P-selectin glycoprotein ligand-1, would improve their trafficking pattern. The selectin pathway recruiter, α-1,3-fucosyltransferase-VI enzyme, significantly increased Treg surface fucosylation (66% vs 8%). In a xenogenic GVHD mouse model, fucosylated Tregs showed prolonged periods of in vivo persistence. When given at a lower dose compared with the untreated Tregs, the murine recipients of fucosylated Tregs maintained weight, had ameliorated clinical GVHD, and improved survival (70% vs 30%; P < .0001). These preclinical data indicate that fucosylated human Tregs is an effective strategy for prevention of GVHD and, as such, warrants consideration for future clinical trials.


Clinical and genetic analysis of a Korean patient with X-linked chondrodysplasia punctata: identification of a novel splicing mutation in the ARSE gene.
X-linked recessive chondrodysplasia punctata (CDPX1) is a rare congenital disorder of bone and cartilage development, characterized by punctate calcification in areas of endochondral bone formation, leading to stippled epiphyses, severe nasal and midfacial hypoplasia, short stature, and brachytelephalangy. CDPX1 is caused by mutations in the arylsulfatase E (ARSE) gene located on chromosome Xp22.3. Although most affected males have milder symptoms, some have significant medical problems including respiratory compromise and cervical spinal stenosis due to dysplastic vertebrae. Herein, we present the case of a male infant with the characteristic features of CDPX1 and severe spinal cord compression. Direct sequencing analysis revealed a novel variation (c.430G>A) in the ARSE gene that was thought to be a missense mutation (p.Gly144Arg), but proved to be a novel splicing mutation (r.[430g>a; 430_431ins430+1_430+21) adding seven amino acids between p.Ile143 and p.Gly144 (p.Ile143_Gly-144insSerMetTyrValPheLysSer). This report expands the spectrum of mutations of the ARSE gene and, to the best of our knowledge, is the first clinically and genetically confirmed case of CDPX1 with severe spinal cord compression in Korea.


Interaction of G-actin with thymosin beta 4 and its variants thymosin beta 9 and thymosin beta met9.
Thymosin beta 4 is a major actin sequestering peptide in vertebrate cells and plays a role in the regulation of actin monomer/polymer ratio. Thymosin beta 9 and thymosin beta met9 are minor variants of thymosin beta 4. The possible function of these peptides has been investigated by comparing the actin binding properties of these beta-thymosins. Thymosin beta 9 and thymosin beta met9 were found to inhibit polymerization of ATP-actin with identical KDs of 0.7-0.8 microM (as compared to 2 +/- 0.3 microM for thymosin beta 4); like thymosin beta 4, they bound to ADP-G-actin with a 100-fold lower affinity than to ATP-G-actin. The interaction of thymosin beta 4 and thymosin beta met9 with G-actin was weakened 20-fold upon oxidation of methionine-6 into methionine sulfoxide. Binding of thymosin beta 4 to G-actin was accompanied by a 15% increase in the fluorescence intensity of actin tryptophans, and a 10 nm emission blue shift. Methionine-6 played an important role in this effect. The fluorescence change was used to monitor the kinetics of thymosin beta 4 binding to G-actin in the stopped-flow. The reaction was bimolecular, with association and dissociation rate constants of approximately 1.5 microM-1 s-1 and 2 s-1 respectively, under physiological conditions. The possible physiological significances of methionine-6 oxidation and of the relatively slow binding kinetics in regulating thymosin beta 4 function in vivo is discussed.


Asymmetric dimethylarginine predicts appropriate implantable cardioverter-defibrillator intervention in patients with left ventricular dysfunction.
More precise characterization of risk factors for occurring ventricular arrhythmia in patients (pts) with primary prevention implantable cardioverter-defibrillator (ICD) therapy is critical. We sought to investigate whether biomarkers of nitric oxide metabolism can predict the occurrence of ventricular tachyarrhythmias and might be used as risk markers in these pts. Plasma levels of l-arginine (Arg), asymmetric dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), monomethyl l-arginine, and nitrite/nitrate were examined in 106 consecutive pts (mean age 65 years, 97 male, mean LV-EF 24 ± 6%), with ischaemic (n= 82) or non-ischaemic cardiomyopathy (n= 24) who underwent ICD implantation for primary prevention of SCD. Appropriate ICD intervention was assessed during a mean follow-up of 344 days, and occurred in 18 of 106 (17%) pts. Asymmetric dimethylarginine plasma levels were significantly higher in pts with appropriate ICD intervention compared with those without any ICD intervention (0.564 ± 0.083 μmol/L vs. 0.513 ± 0.088 μmol; P= 0.027). The Arg/ADMA ratio was found lower in pts with appropriate ICD intervention than in those without ICD intervention (144.71 ± 32.50 vs. 175.29 ± 41.29; P= 0.002). Univariate Cox regression showed that ADMA (P = 0.028) and the Arg/ADMA ratio (P = 0.003) were associated with a higher incidence of appropriate ICD intervention. In a multivariable Cox regression analysis, an ADMA concentration above the 50th centile was independently associated with appropriate ICD intervention, revealing a hazard ratio (HR) of 4.21 (CI 95 %: 1.14-15.63; P = 0.028, Table 4). An Arg/ADMA ratio below the 25th centile had a HR of 3.83 (1.360-10.87; P = 0.011). Asymmetric dimethylarginine and the Arg/ADMA ratio seem to be new biomarkers for the prediction of ventricular tachycardia/ventricular fibrillation episodes and of appropriate ICD intervention in pts with left ventricular ejection fraction dysfunction (LV-EF ≤ 35%), suggesting a value for risk stratification in these pts.


Children's capacity to agree to psychological research: knowledge of risks and benefits and voluntariness.
A series of studies investigated the capacity of children between the ages of 7 and 12 to give free and informed consent to participation in psychological research. Children were reasonably accurate in describing the purpose of studies, but many did not understand the possible benefits or especially the possible risks of participating. In several studies children's consent was not affected by the knowledge that their parents had given their permission or by the parents saying that they would not be upset if the children refused. In contrast, other studies found that children were much more likely to stop their participation if the experimenter said explicitly that she would not be upset if they stopped. We suggest that experimenters should pay more attention to describing the possible risks and benefits of participation in research, and that they should also make it clearer to children that they are free to stop once they have begun.


Maternal diabetes and its cell membrane abnormalities as they affect the foetus: implications for the mother and birth defects.
My brief is to discuss maternal diabetes and its implications for birth defects. The perinatal mortality in Britain has fallen in the last 70 years from 60 per 1000 live births to less than 10. For the baby of the diabetic mother there has been a more dramatic decrease from 249 per thousand live births reported by Peel and Oakley in 1949 to approximately 30 in the Swedish cohort in 1993. However even in countries such as Sweden with one of the lowest figures there is still a three fold higher perinatal mortality for the baby of the diabetic mother compared with the background population. There has been a much less dramatic decrease in the incidence of congenital malformations. Peel and Oakley reported an incidence of 6.9% in 1949, and Hanson from Sweden in 1993 reported only a marginally lower incidence of 6.1%. Recent observations indicate that gestational diabetes (GDM) may be associated with increased incidence of fetal malformation and perinatal mortality. The most frequent and significant morbidity is fetal macrosomia, which in turn is associated with increased risk of birth injuries and asphyxia, (Persson and Hanson. 1998). Detection and definition of congenital malformation vary but in spite of this and the much better maternal diabetic control, congenital malformation today forms a major cause of the perinatal morbidity and mortality.


[Establishment of finite element model of varus-type ankle arthritis and biomechanical analysis of different correction models for tibial anterior surface angle].
To establish the finite element model of varus-type ankle arthritis and to implement the finite element mechanical analysis of different correction models for tibial anterior surface angle (TAS) in supramalleolar osteotomy. A female patient with left varus-type ankle arthritis (Takakura stage Ⅱ, TAS 78°) was taken as the study object. Based on the CT data, the three-dimensional model of varus-type ankle arthritis (TAS 78°) and different TAS correction models [normal (TAS 89°), 5° valgus (TAS 94°), and 10° valgus (TAS 99°)] were created by software Mimics 21.0, Geomagic Wrap 2021, Solidworks 2017, and Workbench 17.0. The 290 N vertical downward force was applied to the upper surface of the tibia and 60 N vertical downward force to the upper surface of the fibula. Von Mises stress distribution and stress peak were calculated. The finite element model of normal TAS was basically consistent with biomechanics of the foot. According to biomechanical analysis, the maximum stress of the varus model appeared in the medial tibiotalar joint surface and the medial part of the top tibiotalar joint surface. The stress distribution of talofibular joint surface and the lateral part of the top tibiotalar joint surface were uniform. In the normal model, the stress distributions of the talofibular joint surface and the tibiotalar joint surface were uniform, and no obvious stress concentration was observed. The maximum stress in the 5° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress distribution of medial tibiotalar joint surface was uniform. The maximum stress of the 10° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress on the medial tibiotalar joint surface increased. With the increase of valgus, the stress of ankle joint gradually shift outwards, and the stress concentration tends to appear. There was no obvious obstruction of fibula with 10° TAS correction. However, when TAS correction exceeds 10° and continues to increase, the obstruction effect of fibula becomes increasingly significant.


Three-Dimensional Anisotropic Metamaterials as Triaxial Optical Inclinometers.
Split-ring resonators (SRRs) present an attractive avenue for the development of micro/nano scale inclinometers for applications like medical microbots, military hardware, and nanosatellite systems. However, the 180° isotropy of their two-dimensional structure presents a major hurdle. In this paper, we present the design of a three-dimensional (3D) anisotropic SRR functioning as a microscale inclinometer enabling it to remotely sense rotations from 0° to 360° along all three axes (X, Y, and Z), by employing the geometric property of a 3D structure. The completely polymeric composition of the cubic structure renders it transparent to the Terahertz (THz) light, providing a transmission response of the tilted SRRs patterned on its surface that is free of any distortion, coupling, and does not converge to a single point for two different angular positions. Fabrication, simulation, and measurement data have been presented to demonstrate the superior performance of the 3D micro devices.


Perforations following endoscopic retrograde cholangiopancreatography: a single institution experience and surgical recommendations.
Perforation after endoscopic retrograde cholangiopancreatography (ERCP) is uncommon, and its management is dependent on the mechanism and the graded classification of injury. Records of patients undergoing ERCP were analyzed over a 16-year period, patterning the types of injuries, diagnosis, management, and patient outcome. Type I injuries damage the medial or lateral duodenal wall before sphincter cannulation. Type II injuries are periampullary and occur as a result of a precut or a papillotomy. Type III injuries occur secondary to guidewire insertion or stone extraction from the common bile duct. Type IV injuries are probably microperforations that are noted on excessive insufflation during and after ERCP withdrawal. Between 1995 and 2011, 27 perforations were identified from 1,638 ERCP procedures (1.6%). Nearly half of the procedures were regarded as difficult by the endoscopist, with 70% of the ERCPs (19 of 27) being for therapeutic indications. There were 5 type I, 12 type II, 5 type III, and 5 type IV perforations, of which 18 cases were diagnosed at the time of ERCP. Delayed diagnosis of type I perforations that were associated with free intraperitoneal air and contrast leakage proved fatal. Most type II perforations required immediate surgery with pyloric exclusion; delayed surgery with simple drainage had a high mortality rate. Most type III and type IV injuries can successfully be managed conservatively without delayed sepsis. In perforation, the mechanism of injury during ERCP predicts the need for surgical management. Type I and type II injuries require early diagnosis and aggressive surgery, whereas type III and type IV injuries may be managed conservatively.


Direct Observation: Assessing Orthopaedic Trainee Competence in the Ambulatory Setting.
The Accreditation Council of Graduate Medical Education requires that residency programs teach and assess trainees in six core competencies. Assessments are imperative to determine trainee competence and to ensure that excellent care is provided to all patients. A structured, direct observation program is feasible for assessing nontechnical core competencies and providing trainees with immediate constructive feedback. Direct observation of residents in the outpatient setting by trained faculty allows assessment of each core competency. Checklists are used to document residents' basic communication skills, clinical reasoning, physical examination methods, and medical record keeping. Faculty concerns regarding residents' professionalism, medical knowledge, fatigue, or ability to self-assess are tracked. Serial observations allow for the reinforcement and/or monitoring of skills and attitudes identified as needing improvement. Residents who require additional coaching are identified early in training. Progress in educational milestones is recorded, allowing an individualized educational program that ensures that future orthopaedic surgeons excel across all domains of medical and surgical competence.


[Leukocytoclastic vasculitis].
Leukocytoclastic vasculitis (LcV) is the most common form of cutaneous vasculitis. Often LcV results from deposition of immune complexes in the vascular wall. When IgA is the dominant immunoglobulin in these complexes, systemic involvement is likely (Henoch-Schönlein purpura), being more severe in adults. LcV in which immune complexes are composed of IgG or IgM are more often limited to the skin and may additionally show minor systemic involvement. In other forms of LcV additional pathophysiological factors play a role. LcV can also be a presenting or accompanying symptom of severe systemic ANCA-associated vasculitis. In some cases, LcV is a sign of bacteriemia. The aim of diagnostic procedures is to determine the specific type of vasculitis and degree of systemic involvement as well as possible causes. If no trigger or cause can be found, uncomplicated cases of LcV should be treated symptomatically. Corticosteroids are indicated at initial signs of necrosis or ulceration. Chronic recurrent LcV may respond to dapsone or colchicine. Severe systemic vasculitis requires immunosuppressive therapy.


Fermented Gluten-Free Multi-Grain Cereal Paste Development: The Role of the Orange-Fleshed Sweet Potato (OFSP) as a Dietary Supplement.
Vitamin A deficiencies is a becoming persistent among young children and a growing concern to parents in sub-Saharan Africa, especially in crisis-affected areas. Fermented cereal paste from maize, millets, and sorghum grains are significant food for young children. Thus, the study focuses on food fortification using orange-fleshed sweet potato (OFSP) as fortifier as studies have confirmed the presence of nutrients that can help meet the Vitamin A dietary requirement. The cereals were soaked ambient temperature (27 ± 1°C) for 72 hours and were blended with OFSP (90:10, 80:20, 70:30, 60:40, 50:50), and the formulated products were studied for Vitamin A, β-carotene, proximate composition, physicochemical, functional properties, and storage. Application of OFSP as forticant increased the Vitamin A (4.98-6.65 mg/100 g), β-carotene (0.10-0.17 mg/100 g) and the calorific value (222.03-301.75 kcal) of the gluten-free multi-grain cereal paste. The addition of OFSP also increased the ash content (1.41%-3.35%), crude fiber (2.56%-4.225%), carbohydrate (39.83%-48.35%), total solid content (55.20%-60.87%), and water absorption capacity (112.20%-137.49%) of the formulated cereal samples. The fortified fermented paste was objectively stable throughout on the shelf from the storage studies. The study deduced that addition of orange-fleshed sweet potato to fermented mixed cereal paste as a fortifier can help increase the nutritional quality of the complementary food.


RAPD analyses of recombination processes in the entomopathogenic fungus Beauveria bassiana.
To understand the nature of recombination processes in Beauveria bassiana, double-auxotrophic complementary mutant strains were used to produce six heterokaryons by three different methods. Conidia from these heterokaryons were plated on selective media and stable haploid (but not diploid) recombinants were isolated. Single colony recombinants were recovered with both parental and non-parental random amplified polymorphic DNA (RAPD) profiles. These results suggest that a range of different recombination mechanisms may be occurring in B. bassiana.


Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension.
In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt (MCT+Flow). The shunt is created by inserting an 18-G needle from the abdominal aorta into the adjacent caval vein. Increased pulmonary flow has been demonstrated as an essential trigger for a severe form of PAH with distinct phases of disease progression, characterized by early medial hypertrophy followed by neointimal lesions and the progressive occlusion of the small pulmonary vessels. To measure the right heart and pulmonary hemodynamics in this model, right heart catheterization is performed by inserting a rigid cannula containing a flexible ball-tip catheter via the right jugular vein into the right ventricle. The catheter is then advanced into the main and the more distal pulmonary arteries. The histopathology of the pulmonary vasculature is assessed qualitatively, by scoring the pre- and intra-acinar vessels on the degree of muscularization and the presence of a neointima, and quantitatively, by measuring the wall thickness, the wall-lumen ratios, and the occlusion score.


The effect of aldicarb on nematode population and its persistence in carrots, soil and hydroponic solution.
Aldicarb, Temik 15 G, was incorporated in furrows at 3.37 and 6.73 kg ai (active ingredient)/ha and carrots (Daucus carota L.) were directly seeded on the same day. The numbers of nematode larvae were significantly suppressed in the treated plots; averages were 249, 74, and 51/50 cc soil samples for control (0), 3.37 and 6.73 kg ai/ha, respectively. Aldicarb treatment resulted in a 28% yield increase as compared to the untreated. Aldicarb residue in carrots was 28 ppb for the low treatment and 46 ppb for the high. Residual levels in soil of high treatment declined from 61 to 31 ppb during two weeks prior to harvest, meanwhile, those in the low decreased slightly from 13 to 12 ppb. Carrots placed in hydroponic solution containing aldicarb 14.5 ppm for 6 days, had an aldicarb residue of 10.26 ppb and the hydroponic solution, 2.7 ppb. Persistence of aldicarb residue was in carrot greater than in soil greater than in hydroponic solution.


Immunologic and molecular evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical remission phase.
This study evaluates residual disease in 28 B-cell chronic lymphocytic leukemia (B-CLL) patients who obtained a clinicohematologic remission after intensive chemotherapy. Sixteen of 28 patients (57%) showed a normal number of circulating B-lymphocytes, as demonstrated by the low percentage of mouse rosette-forming cells (M-RFC), surface immunoglobulins (SIg), and CD24-positive cells. Clinically, a lower number of relapses occurred in this group of patients compared to those with a persistent expansion of peripheral B-cells (P less than 0.05). In order to assess monoclonality of the residual peripheral B-cell population, the distribution of SIg light chains was investigated on the B-cell-enriched fraction of 15 of these 16 cases. Only six of them had a kappa/lambda ratio which ranged between 1.7:1 and 3:1, whereas the remaining patients still displayed a clearly imbalanced kappa/lambda Ig light chain distribution. On the other hand, the analysis of the configuration of the Ig heavy chain gene region, performed in nine cases (including five of the above six cases), showed the persistence of a rearranged pattern in all cases tested but one. Therefore, residual monoclonal B-cells were found also in the majority of cases which displayed the lowest kappa/lambda ratio, a normal bone marrow lymphocytosis and a long-lasting clinical remission. Studies at the DNA level confirm that a remission is rarely achieved in this disease in spite of intensive and prolonged chemotherapy. Nonetheless, the follow-up of B-CLL patients by conventional immunologic markers may be helpful to better define response to therapy and to predict the occurrence of clinical relapse.


MicroRNAs in DNA Damage Response, Carcinogenesis, and Chemoresistance.
In the classical model of tumorigenesis, cancer develops via slowly accumulating mutations that facilitate uncontrolled cell growth and allow cells to escape apoptosis. Oncogenes and tumor suppressor genes regulate the key signaling pathways involved in tumorigenesis and cancer progression. Moreover, studies indicate that MicroRNAs (MiRNAs) are also key parts of these processes. MiRNAs are short, noncoding RNAs that regulate the expression of target genes at the posttranscriptional level. By regulating the expression of numerous cytokines, MiRNAs play crucial roles in cell growth, apoptosis, and stemness maintenance. Abundant evidence demonstrates that MiRNAs can function as both oncogenes and tumor suppressors in accommodating the proliferation and invasion of cancer cells in solid tumors. Targeting these MiRNAs may significantly alter oncogenic signaling pathways and slow or halt progression of many different types of tumors. A better understanding of the functions of MiRNAs in cancer will enable the development of new treatment strategies for chemoresistant malignancies. This review discusses recent findings about the connections between MiRNAs and carcinogenesis and provides insight into the role of MiRNAs in generating chemoresistance.


Machine learning with optimization to create medicine intake schedules for Parkinson's disease patients.
This paper presents a solution for creating individualized medicine intake schedules for Parkinson's disease patients. Dosing medicine in Parkinson's disease is a difficult and a time-consuming task and wrongly assigned therapy affects patient's quality of life making the disease more uncomfortable. The method presented in this paper may decrease errors in therapy and time required to establish a suitable medicine intake schedule by using objective measures to predict patient's response to medication. Firstly, it demonstrates the use of machine learning models to predict the patient's medicine response based on their state evaluation acquired during examination with biomedical sensors. Two architectures, a multilayer perceptron and a deep neural network with LSTM cells are proposed to evaluate the patient's future state based on their past condition and medication history, with the best patient-specific models achieving R2 value exceeding 0.96. These models serve as a foundation for conventional optimization, specifically genetic algorithm and differential evolution. These methods are applied to find optimal medicine intake schedules for patient's daily routine, resulting in a 7% reduction in the objective function value compared to existing approaches. To achieve this goal and be able to adapt the schedule during the day, reinforcement learning is also utilized. An agent is trained to suggest medicine doses that maintain the patient in an optimal state. The conducted experiments demonstrate that machine learning models can effectively model a patient's response to medication and both optimization approaches prove capable of finding optimal medicine schedules for patients. With further training on larger datasets from real patients the method has the potential to significantly improve the treatment of Parkinson's disease.


Integration host factor interactions with Neisseria gene sequences: correlation between predicted binding sites and in vitro binding of Neisseria -derived IHF protein.
Putative integration host factor (IHF) binding sites are frequently being identified in Neisseria gene sequences on the basis of similarity to a degenerate Escherichia coli -derived consensus binding sequence. In this report, three different Neisseria genetic systems that contain predicted IHF binding sites were assessed for IHF binding through gel retardation analysis. The results show a positive correlation between the identification of a predicted Neisseria IHF binding site and in vitro binding of Neisseria -derived IHF protein.