Correction of pulmonary atresia with ventricular septal defect in the absence of the pulmonary trunk and the central pulmonary arteries (so-called truncus type IV).
A child with pulmonary atresia and ventricular septal defect and no extraparenchymal pulmonary arteries had all the bronchopulmonary arterial segments connected to naturally occurring systemic-pulmonary collaterals. A three-staged surgical correction was performed. At the first and second stages, the arteries of each hilus were interconnected with synthetic arteries. At the third stage, the ventricular septal defect was closed, and continuity between the right ventricle and the bilateral pulmonary circulation was established with a valved conduit giving rise to a side arm. Postoperative evolution was good, with acceptable postrepair per right ventricular--left ventricular pressure ratio.


[RESEARCH PROGRESS OF CONSTRUCTING INJECTABLE TISSUE ENGINEERED ADIPOSE TISSUE WITH ADIPOSE-DERIVED STEM CELLS].
To review the research progress of constructing injectable tissue engineered adipose tissue by adipose-derived stem cells (ADSCs). Recent literature about ADSCs composite three-dimensional scaffold to construct injectable tissue engineered adipose tissue is summarized, mainly on the characteristics of ADSCs, innovation of injectable scaffold, and methods to promote blood supply. ADSCs have a sufficient amount and powerful ability such as secretion, excellent compatibility with injectable scaffold, plus with methods of promoting blood supply, which can build forms of injectable tissue engineered adipose tissue. In despite of many problems to be dealt with, ADSCs constructing injectable tissue engineered adipose tissue may provide a promising source for soft-tissue defect repair and plastic surgery.


Mechanical evaluation of a soft tissue interference screw with a small diameter: significance of graft/bone tunnel cross-sectional area ratio.
The purpose of this study is to evaluate the mechanical properties of a graft fixation using a small diameter soft tissue interference screw and analyze the factors affecting the fixation strength. Forty porcine knees were used. A bone tunnel, either 4.5 mm (n=40) or 5.0 mm (n=40) in diameter, was created in the bone block obtained from the proximal tibia or the distal femur. A patella-patellar tendon specimen with varied width was harvested, and the distal end of the patellar tendon was fixed within the bone tunnel using a small diameter soft tissue interference screw (4 x 15 mm). Then, the patella-patellar tendon-bone block complex was loaded until failure occurred and the maximum load was measured. As potential influential factors on the fixation strength, the insertion torque, bone mineral density of the bone block, and graft/tunnel cross-sectional area ratio (GTR) of each specimen were calculated. A significant correlation between the maximum failure load and the insertion torque was demonstrated. The quadratic regression analysis showed a statistically significant correlation between the failure load and the GTR. Optimal GTR for achieving high fixation strength was approximately 80%. When used in appropriate conditions, the mean failure load was 177 N for the 4.5 mm screw and 180 N for the 5 mm screw. The use of a small diameter interference screw for the fixation of a tendon graft to a bone is clinically feasible. Our research showed that the selection of appropriate fitting conditions is an important factor for optimizing the properties of the fixation.


Integrating spiritual care into nursing education and practice: Strategies utilizing Open Journey Theory.
Throughout nursing, spirituality is a recognized domain of patient care, but nurses feel ill prepared by their nursing education to provide care that is spiritual in nature to patients and their families. Incorporating spiritual care into nursing curricula is challenging in light of the amount of topics for healthcare learning. Open Journey Theory is based on the merging of two grounded theories, one teaching and one learning theory, and is the suggested framework for integrating spirituality and spiritual care across all levels of nursing education. Specially chosen readings (books, articles), activities (role-plays, discussion groups), and assignments (journaling, writing papers, giving reports) can be integrated into already existing courses. By utilizing the three stages of preparing, connecting, and reflecting to frame student learning, nurse educators can introduce and build on spiritual concepts from the simple to the complex over the course of the entire nursing program.


Management of penetrating abdominal stab wounds.
The authors present the results of a therapeutic trial of the conservative or surgical management of penetrating abdominal stab wounds (PASW) based on clinical criteria. In a prospective series of 100 patients, 70 were treated non-operatively. Thirty patients were operated upon, twenty-one immediately and nine during the 48 h observation period. In five laparotomies no significant injuries were found. Morbidity was similar in both immediate and delayed laparotomy groups (3/21 versus 1/9). Acute alcoholic intoxication identifies a subgroup of patients that are difficult to evaluate and hence are more likely to be managed by laparotomy (chi 2 = 4.056, P less than 0.05). The authors conclude that selective surgical management of PASW based on clinical criteria is an accurate and safe procedure.


T cell immunity in HSV-1- and VZV-infected neural ganglia.
Herpesviruses hijack the MHC class I (MHC I) and class II (MHC II) antigen-presentation pathways to manipulate immune recognition by T cells. First, we illustrate herpes simplex virus-1 (HSV-1) and varicella-zoster virus (VZV) MHC immune evasion strategies. Next, we describe MHC-T cell interactions in HSV-1- and VZV- infected neural ganglia. Although studies on the topic are scarce, and use different models, most reports indicate that neuronal HSV-1 infection is mainly controlled by CD8+ T cells through noncytolytic mechanisms, whereas VZV seems to be largely controlled through CD4+ T cell-specific immune responses. Autologous human stem-cell-derived in vitro models could substantially aid in elucidating these neuroimmune interactions and are fit for studies on both herpesviruses.


The Transosseous Internal Four Strand Technique: A New All-Inside Technique for Zone 1 Flexor Tendon Repairs.
Multiple techniques for the repair of flexor tendon injuries in zone 1 have been proposed over time. While pull-out suture techniques and bone anchor seem to be stronger than internal suture techniques, they are associated with a higher complication rate. We therefore developed an alternative internal suture repair with similar biomechanical stability to those of pull-out sutures and bone anchors. Twenty porcine distal phalanges and deep flexor tendons were randomized to 2 groups of 10 each. The tendons were transsected at the level of the distal interphalangeal joint. In group 1, repairs were performed with a well-established intraosseous suture repair and in group 2 with our new multistrand technique. The repairs were biomechanically tested with linear distraction until failure. We recorded a significantly higher 2-mm gap force (2GF)-and thus higher stability-of the repairs in group 1 in comparison to group 2. With a 2GF of more than 50 N, our suture technique allows for a modern early active motion rehabilitation protocol. Breakage of the suture construct occurred at random places in the repair in both groups. No pull-outs were noted. This study presents a strong transosseous multistrand repair technique for flexor tendon repair in zone 1 that is simple and fast to perform and should have enough strength to withstand early active motion rehabilitation.


Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study.
Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta-aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. evaluate long-term efficacy and safety of givosiran in acute hepatic porphyria. Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (≥12 years) with recurrent attacks received givosiran (2.5 mg/kg monthly) (n = 48) or placebo (n = 46) for 6 months (double-blind period); 93 received givosiran (2.5 mg or 1.25 mg/kg monthly) in the open-label extension (continuous givosiran, n = 47/48; placebo crossover, n = 46/46). Endpoints included annualized attack rate, urinary delta-aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events. Patients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double-blind period, 0.0 in open-label extension); in placebo crossover patients, median annualized attack rate decreased from 10.7 to 1.4. Median annualized days of hemin use were 0.0 (double-blind period) and 0.0 (open-label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long-term givosiran led to sustained lowering of delta-aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double-blind period. Long-term givosiran has an acceptable safety profile and significantly benefits acute hepatic porphyria patients with recurrent attacks by reducing attack frequency, hemin use, and severity of daily worst pain while improving quality of life.


Using family-centered communication to optimize patient-provider-companion encounters about changing to biosimilars: A randomized controlled trial.
To explore whether family-centered communication impacts decisions and optimizes patient-companion-provider consultations. A parallel, two-arm randomized controlled trial was conducted with 108 participants acting as patients with inflammatory arthritis or companions. Pairs attended a mock consultation where a physician explained the change from a bio-originator to a biosimilar using family-centered or patient-only communication. Participants reported their willingness to transition, risk perceptions, understanding and social support, and completed various scales including the Patient Perception Scale. Interviews helped understand perceptions towards the consultation. Family-centered communication did not impact willingness to change or cognitive risk perceptions compared to patient-only communication. However, it improved emotional risk perceptions (p = 0.047, Cohen's d=.55) and satisfaction with communication (p = 0.015, Cohen's d=.71). Feeling the explanation was reassuring was associated with less worry (p = 0.004). Receiving emotional support (p = 0.014) and companions asking fewer questions (p = 0.046) were associated with higher recall. The intervention improved companion involvement (p < 0.001, Cohen's d= 1.23) and support (p = 0.002, Cohen's d=.86). Interviews showed that encouraging questions, inclusive body language, and acknowledging companions facilitated involvement. Family-centered communication augments patient-companion-provider encounters but does not influence willingness to change treatment. Practitioners can use family-centered communication when discussing biosimilars but should provide reassurance, encourage emotional support, and summarize key points to improve understanding.


Multi-omics reveal microbial determinants impacting the treatment outcome of antidepressants in major depressive disorder.
There is a growing body of evidence suggesting that disturbance of the gut-brain axis may be one of the potential causes of major depressive disorder (MDD). However, the effects of antidepressants on the gut microbiota, and the role of gut microbiota in influencing antidepressant efficacy are still not fully understood. To address this knowledge gap, a multi-omics study was undertaken involving 110 MDD patients treated with escitalopram (ESC) for a period of 12 weeks. This study was conducted within a cohort and compared to a reference group of 166 healthy individuals. It was found that ESC ameliorated abnormal blood metabolism by upregulating MDD-depleted amino acids and downregulating MDD-enriched fatty acids. On the other hand, the use of ESC showed a relatively weak inhibitory effect on the gut microbiota, leading to a reduction in microbial richness and functions. Machine learning-based multi-omics integrative analysis revealed that gut microbiota contributed to the changes in plasma metabolites and was associated with several amino acids such as tryptophan and its gut microbiota-derived metabolite, indole-3-propionic acid (I3PA). Notably, a significant correlation was observed between the baseline microbial richness and clinical remission at week 12. Compared to non-remitters, individuals who achieved remission had a higher baseline microbial richness, a lower dysbiosis score, and a more complex and well-organized community structure and bacterial networks within their microbiota. These findings indicate a more resilient microbiota community in remitters. Furthermore, we also demonstrated that it was not the composition of the gut microbiota itself, but rather the presence of sporulation genes at baseline that could predict the likelihood of clinical remission following ESC treatment. The predictive model based on these genes revealed an area under the curve (AUC) performance metric of 0.71. This study provides valuable insights into the role of the gut microbiota in the mechanism of ESC treatment efficacy for patients with MDD. The findings represent a significant advancement in understanding the intricate relationship among antidepressants, gut microbiota, and the blood metabolome. Additionally, this study offers a microbiota-centered perspective that can potentially improve antidepressant efficacy in clinical practice. By shedding light on the interplay between these factors, this research contributes to our broader understanding of the complex mechanisms underlying the treatment of MDD and opens new avenues for optimizing therapeutic approaches. Video Abstract.


Verrucous carcinoma of the female genital tract: report of a case and review of the literature.
Verrucous carcinoma (VC) of the female genital tract is a rare lesion, primarily affecting postmenopausal women. A case of VC of the vulva is reported, bringing the total number of VC of the female genital tract to 89. VC is a slowly growing, locally "pushing" tumor with a rather benign histologic appearance, and the clinical and histologic characteristics are described on the basis of the present report and a review of the literature. The treatment of VC is still a matter of discussion. It seems logical to treat the tumor by wide local excision, taking the lack of proof of spontaneous metastasis into consideration. Radiation therapy should be contraindicated, and local application of podophyllin, bleomycin therapy, and cryosurgery are ineffective methods in the treatment of VC.


Prostaglandin D2 and histamine during the immediate and the late-phase components of allergic cutaneous responses.
With a skin blister technique in which the mediators generated by the trauma of forming the blister are allowed to subside, we have collected human interstitial skin fluid during the course of allergic reactions to ragweed, and measured levels of histamine and prostaglandin D2 (PGD2). Of 18 ragweed-allergic individuals tested, 11 developed both an immediate and a late-phase reaction (LPR) with fivefold-elevated levels of histamine (40 ng/ml) at 30 minutes and a peak level of PGD2 (6.5 ng/ml) later at 2 1/2 hours after ragweed challenge. The other seven allergic individuals had immediate reactions without an LPR lesion and demonstrated somewhat smaller elevations of histamine (25 ng/ml) but much lower levels of PGD2 (1.6 ng/ml; p less than 0.05). The time course of appearance of these mediators was identical in both groups of patients. The fluids from unchallenged blisters of allergic and nonallergic patients and the fluids of nonallergic patients challenged with ragweed had similar levels of histamine, at the lower limit of detection, and undetectable PGD2 levels. The peak levels of PGD2 in allergic individuals correlated with the size of the LPR lesion (p less than 0.05). These data suggest that the LPR involves the secondary elaboration of mediators different from mediators responsible for the immediate manifestations of the allergic skin reaction.


Structural connectome alterations in anxious dogs: a DTI-based study.
Anxiety and fear are dysfunctional behaviors commonly observed in domesticated dogs. Although dogs and humans share psychopathological similarities, little is known about how dysfunctional fear behaviors are represented in brain networks in dogs diagnosed with anxiety disorders. A combination of diffusion tensor imaging (DTI) and graph theory was used to investigate the underlying structural connections of dysfunctional anxiety in anxious dogs and compared with healthy dogs with normal behavior. The degree of anxiety was assessed using the Canine Behavioral Assessment & Research Questionnaire (C-BARQ), a widely used, validated questionnaire for abnormal behaviors in dogs. Anxious dogs showed significantly decreased clustering coefficient ([Formula: see text]), decreased global efficiency ([Formula: see text]), and increased small-worldness (σ) when compared with healthy dogs. The nodal parameters that differed between the anxious dogs and healthy dogs were mainly located in the posterior part of the brain, including the occipital lobe, posterior cingulate gyrus, hippocampus, mesencephalon, and cerebellum. Furthermore, the nodal degree ([Formula: see text]) of the left cerebellum was significantly negatively correlated with "excitability" in the C-BARQ of anxious dogs. These findings could contribute to the understanding of a disrupted brain structural connectome underlying the pathological mechanisms of anxiety-related disorders in dogs.


Anomalies of motor development in hyperactive boys.
Forty-eight boys who scored high on rating scales for the "hyperactive syndrome" but who went without traditional neurological signs of learning disabilities were compared with 50 control boys on coordination tests. Discriminant function scores for speed, rhythm, and overflow correctly classified 89% of the boys as those with "hyperactive" versus "normal" behavioral histories. Thus, neurological examination of "hyperactive" boys does reveal developmentally immature coordination.


A case of schizophrenia with dysphagia successfully treated by a multidimensional approach.
Dysphagia in patients with psychiatric illnesses contributes to morbidities and mortalities. It is, however, an overlooked problem in clinical practice. We report a patient of schizophrenia with dysphagia who was successfully treated using a multidimensional approach, which included medication adjustment, swallowing training and diet modification.


Distribution of the 36 000 dalton tyrosine protein kinase substrate in drug and epidermal growth factor-treated epithelial cells.
In immunofluorescent staining the 36 000 D substrate protein (p36) of epidermal growth factor (EGF)-induced tyrosine phosphorylation is distributed relatively homogeneously in non-tumorigenic MMC-E epithelial cells. A relative lack of p36 staining is found in the nuclease and along ventral microfilament bundles of the cells. Increased concentrations of p36 are detected at the cell surface and especially at cell-cell contact sites. The bulk of p36 antigen is not redistributed by drug treatments that selectively redistribute cytokeratin, or disrupt microtubules or actin microfilaments. The gross distribution of p36 is neither affected by EGF stimulation nor by the associated rapid morphological and cytoskeletal changes. It thus appears unlikely that p36 would be a structural component of the cytoskeletal system of cultured epithelial cells.


Dietary cadmium health risk assessment for the Chinese population.
Cadmium (Cd) has high rates of soil-to-plant transference, coupled with its non-biodegradability and persistence; long-term management of Cd in agriculture is thus required to ensure better soil and food security and safety. Identifications of regions with high soil Cd concentration or high dietary Cd intakes are critical public health priorities. Human health risk assessment for dietary Cd intake was thus undertaken by employing three approaches: FCA (food chain approach), TDA (total diet approach), and FQA (food quality approach). The correlation between green/total vegetable consumption rates and dietary Cd intake from vegetables was statistically significant. For consumption, the hazard quotients (HQs) calculated by FCA and TDA were all less than 1 except for Hunan and Sichuan province. For rice consumption, the HQs derived by FCA or TDA approach for eight provinces exceeded 1. Residents in Hubei, Guangxi, Jilin, Zhejiang, Liaoning, Shanghai, Sichuan, and Guangxi were more vulnerable due to their notable higher consumption rates.Weighted rankings of the health risk levels were determined to derive the comparative risk management priority. For Cd intake from vegetables, four provinces/cities have high relative priority; for Cd intake from grains, three provinces have high relative priority. The comparative risk management priority for Hunan and Sichuan was high for dietary intake from vegetables or rice. Weighted average HQs were derived to determine the integrated dietary Cd intake health risk levels for dietary intake from vegetables or grains. The risk levels for Hunan, Guangxi, Sichuan, and Zhejiang are high, so effective measures should be taken to reduce Cd dietary intakes to ensure health protection.It is envisaged that the methodology employed in this study could provide useful insights into how various approaches can be integrated to determine human health risk levels for Cd intake, so more effective and targeted measures can be taken accordingly for the relevant regions.


TREM2: Keeping Microglia Fit during Good Times and Bad.
Microglia are the macrophages of the brain and play an important role in Alzheimer's disease (AD). In Cell, Ulland et al. (2017) recently reported that mutations in TREM2, a protein implicated in AD, disrupt microglial energy state and function, thus sabotaging the microglia's ability to defend the brain against amyloid plaques.


Seasonal variation in Laminaria digitata and its impact on biochemical conversion routes to biofuels.
Laminaria digitata is a highly prevalent kelp growing off the coast of the UK but has rarely been considered as a source of biomass to date. This study shows it can be used as a feedstock in both ethanol fermentation and anaerobic digestion for methane production. The study optimised several parameters in the fermentation of L. digitata and investigated the suitability of the macroalgae through the year using samples harvested every month. For both methane and ethanol production, minimum yields were seen in material harvested in March when the carbohydrates laminarin and mannitol were lowest. July material contained the highest combined laminarin and mannitol content and maximum yields of 167 mL ethanol and 0.219 m(3) kg(-1)L. digitata.


Secundum atrial septal defect and cleft mitral valve.
The association of a secundum atrial septal defect and mitral insufficiency is not uncommon. Five patients with this combination of lesions are presented and the pathological anatomy of the mitral valve is discussed. All 5 patients demonstrated a similar cleft mitral valve; 2 had cleft valves when only mitral valve prolapse was suspected preoperatively. The surgical implication of these lesions is discussed.


Ophthalmic manifestations of Aarskog (facial-digital-genital) syndrome.
Four boys with facial-digital-genital or Aarskog syndrome were whort with triangular faces, characteristic deformities of the hands and feet, and anomalies of the external genitalia. The syndrome appears to be inherited in an X-chromosomes-limked recessive manner. Previous reports emphasized the presence of hypertelorism but careful measurements of the interorbital dimensions revealed primary telecanthus in addition to hypertelorism. The palpebral fissures had a marked antimongoloid obliquity and in half the reported cases, there was unilateral or bilateral congenital blepharoptosis. Strabismus, hyperopic astigmatism, and large corneas may be additional features.


Meiotic recombination and genome evolution in plants.
Homologous recombination affects genome evolution through crossover, gene conversion and point mutations. Whole genome sequencing together with a detailed epigenome analysis have shed new light on our understanding of how meiotic recombination shapes plant genes and genome structure. Crossover events are associated with DNA sequence motifs, together with an open chromatin signature (hypomethylated CpGs, low nucleosome occupancy or specific histone modifications). The crossover landscape may differ between male and female meiocytes and between species. At the gene level, crossovers occur preferentially in promoter regions in Arabidopsis. In recent years, there is rising support suggesting that biased mismatch repair during meiotic recombination may increase GC content genome-wide and may be responsible for the GC content gradient found in many plant genes.


Distribution characteristics and risk assessment of neonicotinoid insecticides in planting soils of mainland China.
Neonicotinoid insecticides (NEOs) are generally used in crop production. Their widespread use on agricultural soil has raised concerns regarding their health and ecological risks. Previous studies have reported the contamination of the farmland soils with NEOs from the coastal provinces of China. Information about NEOs at the national scale as well as the residues of their metabolites are relatively unknown. In this study, 391 soil samples were collected from 31 provinces in nine agricultural regions across mainland China, and the concentrations of ten parent NEOs and three metabolites were determined. At least one NEO was detected in all soil samples, with the sum of the NEOs (ΣNEOs) ranging from 0.04 to 702 μg/kg. The most common parent NEO and metabolite are imidacloprid and imidacloprid-urea, respectively. The concentrations of NEOs in coastal regions at the same latitude were higher than those in inland regions. The NEOs were further compared in the soils of seven types of monocrops and three types of multiple crops (multicrops) (i.e., two types of crops were produced in succession or simultaneously within the decade of this study). The results showed that the highest NEO residues were found in soils planted with vegetables (VE), fruits (FR), and cotton (CO) monocrops and VE & FR multicrops. Differences in NEO concentrations were observed between soils planted with monocrops and multicrops. For example, VE & FR > VE > vegetables and grains (VE & GR) > GR. Moreover, the health risks posed by NEOs in agricultural soils in China are extremely low, and the ecological risks require urgent attention. Particularly, individual NEOs in > 45% of agricultural soils in mainland China may have sublethal effects on two non-target species (HQnon-target > 0.01).


[Business intelligence in radiology. Challenges and opportunities].
Due to economic pressures and need for higher transparency, a ubiquitous availability of administrative information is needed. Therefore radiology managers should consider implementing business intelligence (BI) solutions. BI is defined as a systemic approach to support decision-making in business administration. It is an important part of the overall strategy of an organization. Implementation and operation is initially associated with costs and for a successful launch important prerequisites must be fulfilled. First, a suitable product must be selected, followed by the technical and organizational implementation. After consideration of the type of data to be collected and a system of key performance indicators must be established. BI replaces classic retrospective business reporting with multidimensional and multifactorial analyses, real-time monitoring, and predictive analyses. The benefits of BI include the rapid availability of important information and the depth of possible data analysis. The simple and intuitive use of modern BI applications by the users themselves (!) combined with a continuous availability of information is the key to success. Professional BI will be an important part of management in radiology in the future.


Antimicrobial and wound healing activities of certain Sudanese medicinal plants.
The emergence of drug-resistant organisms have been increasing globally; therefore, it is a burning need to find an alternative drug to get rid of the diseases caused by resistant strains. This study aims to evaluate the antimicrobial and wound healing activities of Loranthus acacia, Cassia obtusifolia and Cymbopogon proximus plants. All the plants were collected and extracted - by maceration method. Antimicrobial activities determined using standard ATCC strain for Gram-positive bacteria (Bacillus subtilis, Bacillus crew, Methicillin-resistant Staphylococcus aureus, Staphylococcus aureus) and Gram-negative bacteria (Shigella sonnnei, Salmonella Typhimurium, Salmonella typhi, Klebsiella pnuemoniae, Escherichia coli and Pseudomonas aeruginosa) following agar well diffusion method. Plants extracts were prepared as gel and investigated for in vivo wound healing activities in rats. Histological studies were performed on animals' skin. The results showed that all tested plants have various antimicrobial and wound healing activities. Out of these plants, L. acacia exhibited the best result; it revealed a significant result for antimicrobial activities counter to all Gram-positive, Gram-negative bacteria and wound healing activities in comparing with the reference drug. Thus, it is essential to consider L. acacia as a prospective source in progress in the synthesis of a new antimicrobial drug for the treatment of infectious diseases.


Occurrence of anthelmintic resistant equine cyathostome populations in central and southern Italy.
In the present survey, 276 horses bred on 16 farms located in central and southern Italy were investigated for the presence of drug resistant cyathostomes by a Fecal Egg Count Reduction Test (FECRT). Sixteen to 20 animals were selected on each farm and randomly assigned to one of four equally sized treatment groups. Groups were treated with fenbendazole, pyrantel pamoate, ivermectin or moxidectin. Resistance to fenbendazole was declared on six farms (37.5%) and suspected in two farms (12.5%), with FECR values ranging from 41% to 88.3%. Resistance to pyrantel was found in two farms (12.5%) and was suspected in one case (6.2%), with FECR values ranging from 43% to 85.4%. Macrocyclic lactones remained effective on all farms. Only cyathostome third stage larvae (L3) were found in fecal cultures after treatment. This paper reports the first wide survey conducted in Italy for anthelmintic resistance in equine cyathostomes. The results indicate that multiple drug resistant equine cyathostomes are present in the central and southern regions of Italy. These data call for a geographically and numerically broader investigation of horse farms in all regions and for the development and implementation -among veterinarians, owners and managers of a plan to reduce the expansion of these anthelmintic resistant populations and control these important parasites.


Chorea induced by non-ketotic hyperglycaemia: a case report.
We describe an 81-year-old woman presenting with sudden onset of generalised chorea. She was unaware of suffering from diabetes. Laboratory screening revealed non-ketotic hyperglycaemia. Brain magnetic resonance imaging (MRI) failed to show basal ganglia abnormalities. Monotherapy with subcutaneous regular insulin induced a progressive normalisation of glycaemia as well as a parallel improvement of the abnormal involuntary movement scale on a nine-day sequential observation. This correlation strongly supports the hypothesis that non-ketotic hyperglycaemia itself might play a major pathogenetic role in chorea associated with non-ketotic hyperglycaemia. Diabetes mellitus should be suspected in patients who develop sudden onset of chorea even in the absence of putaminal abnormalities on MRI.


Exploring links between pathogen avoidance motivation, COVID-19 case counts, and immune function.
The selection pressures exerted by pathogens have played important roles in shaping the biology and behavior of animals, including humans. Immune systems recognize and respond to cues of infection or damage by coordinating cellular, humoral, and metabolic shifts that promote recovery. Moreover, animals also possess a repertoire of behavioral tools to help combat the threat of pathogens, often referred to as the behavioral immune system. Recently, researchers have begun to examine how cognitive, affective, and behavioral disease avoidance mechanisms interact with the biological immune system. The present study explored relationships among individual differences in behavioral immune system activity (e.g., pathogen disgust), shifts in SARS-CoV-2 infection risk (i.e., 7-day case averages), and immune function in a community cohort from McLennan County, Texas, USA (n = 387). Levels of disease concern were not consistently associated with immune markers. However, serum levels of IFN-γ, TNF-α, IL-2, and IL-8, as well as serum killing ability of Escherichia coli, each varied with case counts. Additional analyses found that case counts also predicted changes in stress physiology, but not subjective measures of distress. However, follow-up mediation models did not provide evidence that relationships between case counts and immunological outcomes were mediated through levels of stress. The present project provides initial evidence that markers of immune function may be sensitive to changes in infection risk during the COVID-19 pandemic. This adds to the growing body of research finding relationships among behavioral and biological pathogen management mechanisms.


Microbial water relations. Effects of solute concentration on the respiratory activity of sugar-tolerant and non-tolerant yeasts.
The respiratory activity of the sugar-tolerant (osmophilic) yeast, Saccharomyces rouxii, and the non-tolerant species, Sacchromyces cerevisiae, were compared after growth in a complex basal medium, the medium supplemented with polyethylene glycol (mol. wt 200) to give a water activity of 0-95, and the medium supplemented with glucose (24 and 36%, w/v). The properties compared were Qo2 (glucose), NADH oxidase activity of isolated mitochondrial fractions, and cytochrome content. When grown in the basal medium S. cerevisiae was somewhat more active than S. rouxii by all criteria. Growth in the media supplemented were high glucose concentrations produced catabolite repression of respiration in S. cerevisiae but not in S. rouxii. The implications of this difference for polyol biosynthesis and the water relations of the sugar-tolerant species are discussed.


Second degree His-Purkinje block during his bundle pacing.
This report presents, for the first time, clear evidence supporting the occurrence of Wenckebach and 2:1 H-V block during His bundle pacing. The simultaneous recording of various intracardiac electrograms, as well as the comparison of the effects produced by selective His bundle pacing and high right atrial pacing at the same rates, permitted the identification of conduction disturbances located distal to the paced His bundle site. This could be done although one criterion usually required to diagnose selective His bundle pacing (namely, stimulus-V intervals of constant duration) was not present.


Physiological stress of high NH (4) (+) concentration in water column on the submersed macrophyte Vallisneria Natans L.
The submersed macrophyte, Vallisneria natans L., was cultured in laboratory with NH (4) (+) -enriched tap water (1 mg L(-1) NH(4)-N) for 2 months and the stressful effects of high ammonium (NH (4) (+) ) concentrations in the water column on this species was evaluated. The plant growth was severely inhibited by the NH (4) (+) supplement in the water column. The plant carbon and nitrogen metabolisms were disturbed by the NH (4) (+) supplement as indicated by the accumulation of free amino acids and the depletion of soluble carbohydrates in the plant tissues. The results suggested that high NH (4) (+) concentrations in the water column may hamper the restoration of submersed vegetation in eutrophic lakes.


Immunohistochemical localization of pregnancy-associated plasma protein A in decidua and trophoblast: comparison with human chorionic gonadotrophin and fibrin.
In an immunoperoxidase study, pregnancy-associated placental protein A (PAPP-A) was localized to the cytoplasm of decidual stromal cells, the villous syncytiotrophoblast and on the surface of placental trophoblast. A decidual and a trophoblastic origin is suggested for PAPP-A, and its presence on the surface of the syncytiotrophoblast is interpreted as a possible immunoprotective layer.


Panton-Valentine leukocidin-producing methicillin-Sensitive Staphylococcus aureus as a cause for recurrent, contagious skin infections in young, healthy travelers returned from a tropical country: a new worldwide public health problem?
Skin infections associated with visits to tropical countries are well known. In most of the cases, the infection is caused by Staphylococcus aureus. After a sufficient antibiotic treatment, the skin infections resolve without any sequelae. But several patients suffer from recurrent skin infections. Panton-Valentine leukocidin (PVL) is a cytotoxin produced by S aureus, which is associated with severe necrotic skin lesions and with a high contagiosity.


Experience of practitioners and delivery outcome.
It is commonly believed that the experience of practitioners (time spent in delivery ward) may be helpful in aiding the spontaneous vaginal birth. To check if this opinion is true. In 995 low-risk, full-term, pregnancies resulting in spontaneous labour, multivariate logistic regression analysis was performed, which considered the age, the years of service of the obstetrician and of the midwife, and of both as independent variables. Results The longer the obstetrician (odds ratio 0.779, C.I. 95% 0.653-0.930, p = 0.006) or the midwife has been practising (odds ratio 0.609, C.I. 95% 0.408-0.909, p = 0.015) the less likely is the occurrence of a spontaneous vaginal birth. The combined years of service of the caring doctor/midwife pair appears to have no influence on the outcome of delivery. The chances of an operative vaginal birth increase with the age of the caring obstetrician (odds ratio 1.362, C.I. 95% 1.138-1.630, p = 0.001). The experience of the staff assisting women in labour definitely does not determine the success of deliveries. The skills of each professional category are based on theoretical knowledge that is possibly not being put to use during routine duties, especially by the 'more experienced' practitioners. Additionally, it appears that there is no team work, and decisions are not taken together.


Enzymatic disappearance of hydroxylamine in the presence of GABA.
This paper presents data on the elimination of hydroxylamine from Lupinus albus seeds when they were germinated in the presence of GABA and hydroxylamine. The possibility of an enzymatic reaction. ATP dependent, between GABA and hydroxylamine is discussed. Some kinetic properties from this reaction are studied.


Stem Cell Therapy for Corneal Epithelium Regeneration following Good Manufacturing and Clinical Procedures.
To evaluate outcomes of cultivated limbal epithelial transplantation (CLET) for management of ocular surface failure due to limbal stem cell deficiency (LSCD). Prospective, noncomparative, interventional case series and extensive comparison with recent similar studies. Twenty eyes with LSCD underwent CLET (11 autologous; 9 allogeneic) and were followed up for 3 years. Etiologies were divided into 3 prognostic categories: Group 1, chemical injuries (7 eyes); Group 2, immune-based inflammation (4 eyes); and Group 3, noninflammatory diseases (9 eyes). Intervention. Autologous and allogeneic limbal epithelial cells were cultivated on amniotic membranes and transplanted. Evaluations were based on clinical parameters, survival analysis, and in vivo confocal microscopy (IVCM). European Union Tissues/Cells Directive and good manufacturing procedures were followed. Improved clinical parameters, absence of epithelial defects, and improved central corneal epithelial phenotype. Success rate was 80% at 1-2 years and 75% at 3 years. Autografts and allografts had similar survival. Success rate was significantly lower in prognostic Group 1 (42.9%) than in Groups 2-3 (100% each). All clinical parameters improved substantially. By IVCM, 80% of cases improved in epithelial status. CLET improved corneal epithelium quality, with subsequent improvement in symptoms, quality of life, and vision. These results confirm that CLET is a valid therapy for ocular surface failure.


[Are screws in anterior cervical fusion with bicortical fixation truly inserted bicortically? Retrospective study].
To examine the exact position of screws in anterior cervical fusion that were intended to be bicortically anchored at the time of surgery. A randomly selected, representative sample (26) of our patient series undergoing anterior cervical fusion with bicortical screw fixation (250) during period of 1993-1999 is reviewed in this study with respect to an exact position of the tips of the screws to the posterior vertebral cortex. A total of 109 screws were assessed. The position of 109 screws was assessed using an axial CT scan. On the basis of the distance of the screw tip from the posterior cortex of the vertebra, the screws were divided into several categories: mono- and bicortically anchored. Bicortically inserted screws were statistically evaluated using the confidence interval. Statistical analysis shows that the confidence interval of the screws being bicortically anchored lies between 66.7 and 87.5% (alpha value = 0.01). No screw was introduced more than 3 mm behind the posterior vertebral cortex. Monocortical introduction more than 1.5 mm in front of the cortex was observed in 7 screws (6.4%) in lower cervical spine and cervico-thoracic junction. All the screws that were classified as being too short were introduced in the cervico-thoracical junction or lower cervical spine known for its reduced X-ray transparency. The majority of screws, primarily described as bicortical, indeed penetrated both vertebral cortices. Considering the results of confidence interval for bicortical screw anchoring we conclude that 1 of 4 screws in monosegmental and 2 of 6 screws in bisegmental stabilization could fail to be bicortically inserted. [corrected] Intraoperative methods used for an accurate and safe bicortical screw insertion during anterior cervical fusion, i.e. intraoperative fluoroscopy, peak insertion torgue of the screw and the length measurement of the taped screw canal, are reliable enough to fulfill these goals.


Short-term calorie restriction enhances adult hippocampal neurogenesis and remote fear memory in a Ghsr-dependent manner.
The beneficial effects of calorie restriction (CR) have been described at both organismal and cellular levels in multiple organs. However, our understanding of the causal mediators of such hormesis is poorly understood, particularly in the context of higher brain function. Here, we show that the receptor for the orexigenic hormone acyl-ghrelin, the growth hormone secretagogue receptor (Ghsr), is enriched in the neurogenic niche of the hippocampal dentate gyrus (DG). Acute elevation of acyl-ghrelin levels by injection or by overnight CR, increased DG levels of the neurogenic transcription factor, Egr-1. Two weeks of CR increased the subsequent number of mature newborn neurons in the DG of adult wild-type but not Ghsr(-/-) mice. CR wild-type mice also showed improved remote contextual fear memory. Our findings suggest that Ghsr mediates the beneficial effects of CR on enhancing adult hippocampal neurogenesis and memory.


Increasing Burden of Hepatitis A in Adolescents and Adults and the Need for Long-Term Protection: A Review from the Indian Subcontinent.
Hepatitis A, an acute inflammatory liver disease caused by hepatitis A virus (HAV) infection from close contact with infected people, is highly endemic in the Indian subcontinent. Due to poor sanitary conditions, most of the population is exposed to the virus in childhood. At this age, the disease is asymptomatic and provides life-long protection against the disease. Due to rapid socioeconomic development in some areas, however, pockets of the population are reaching adolescence/adulthood without prior exposure to the virus and are thus susceptible to infection. At these ages, infection carries a higher risk of symptomatic disease and complications including mortality. This review of epidemiology and burden of disease studies in the Indian subcontinent, published since 2005, shows increasing evidence of a shift from high to intermediate endemicity in high-income-typically urban-populations. The prevalence of anti-HAV antibodies (previously reported at > 90%) is lower now in adolescents and young adults (e.g., around 80% in Bangladesh and 55% in 5-15 years in India). As a result, HAV is responsible for more acute viral hepatitis predominantly in this age group (e.g., > 15 years: 3.4% in 1999 to 12.3% in 2003 or high socioeconomic status 13-20 years: 27% in 1999 to 62% in 2003), with a greater clinical and economic burden. Numerous outbreaks due to HAV have been reported [e.g., Sri Lanka (2009-2010): > 13,000 affected; Kashmir (2015-2017): 12 outbreaks; Kerala (2012-2016): 84 outbreaks] from water or food contamination. Due to current shifts in endemicity, a growing proportion of the population is no longer exposed in childhood. As the disease remains highly endemic, it also provides a source for more severe disease in susceptible people at an older age and for outbreaks. Well-tolerated and effective vaccines are available and help prevent disease burden and provide long-term protection. These should now be used more widely to protect more patients from the growing disease burden of hepatitis A. FUNDING: GlaxoSmithKline Biologicals SA. Plain language summary available for this article-please see Fig. 1 and the following link: https://doi.org/10.6084/m9.figshare.9963044.Fig. 1Plain Language Summary. Highlights the context of the article, the endemicity shift and the burden of hepatitis A in adolescents and adults and steps to be taken to address the impact of this disease.


Establishment of a simple and efficient platform for car-t cell generation and expansion: from lentiviral production to in vivo studies.
Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19 + B-cell malignancies in numerous clinical trials. The CAR molecule, which recognizes cell-surface tumor-associated antigen independently of human leukocyte antigen (HLA), is composed by one or more signaling molecules to activate genetically modified T cells for killing, proliferation, and cytokine production. In order to make this treatment available for a larger number of patients, we developed a simple and efficient platform to generate and expand CAR-T cells. Our approach is based on a lentiviral vector composed by a second-generation CAR that signals through a 41BB and CD3-ζ endodomain. In this work, we show a high-level production of the lentiviral vector, which was successfully used to generate CAR-T cells. The CAR-T cells produced were highly cytotoxic and specific against CD19+ cells in vitro and in vivo, being able to fully control disease progression in a xenograft B-cell lymphoma mouse model. Our work demonstrates the feasibility of producing CAR-T cells in an academic context and can serve as a paradigm for similar institutions. Nevertheless, the results presented may contribute favoring the translation of the research to the clinical practice.


A Dual-Channel PPG Readout System With Motion-Tolerant Adaptability for OLED-OPD Sensors.
An adaptive PPG (Photoplethysmography) readout system for a dual-channel OLED-OPD flexible sensor is designed and developed with motion artifact (<1Hz) and ambient lighting interference successfully compensated without any additional motion sensors. The compensation is made possible by adopting multi-feedbacks and an additional reference OPD channel to cancel effectively DC drifts. In result, the quality of measured PPG is improved to the level such that long-time, continuous quality monitoring of bio-sign such as heart rate (HR) is possible. The readout is designed with an auto-programmable band-pass trans-impedance amplifier (TIA) of a 100dbΩ gain with a continuous-type DC-current cancellation loop. The rest of the readout consists of a 0.5 Hz low-pass filter, an additional second-order band-pass filter (0.1-10Hz), a difference amplifier, a motion reference channel, an analog multiplexer, a programmable gain amplifier (PGA), a digital control and a programmable DAC-PWM based auto-intensity tuned OLED driver. The readout is fabricated in an area of 9 mm2 via the TSMC 180nm process. The experiment result shows that the developed OLED-OPD readout senses well as small as 1nA current, with a measured dynamic range >90dB (1nA to 100 µA) and input-referred noise of 0.26 nA/√H, with power consumption of 460µW. The DC drift is successfully reduced to 1% of its average. The accuracy for heart rate is 96%.


Immunoconjugates in the management of hairy cell leukemia.
Hairy cell leukemia (HCL) is an indolent B-cell malignancy effectively treated but not often cured by purine analog therapy; after multiple courses of purine analogs, patients can become purine analog resistant and in need of alternative therapies. Complete remission to single-agent purine analog is often accompanied by minimal residual disease (MRD), residual HCL cells detectable by immunologic methods, considered a risk factor for eventual relapse. Several different non-chemotherapy approaches are being used to target relapsed and refractory HCL, including inhibitors of BRAF, but so far only monoclonal antibody (MAb)-based approaches have been reported to eliminate MRD in a high percentage of patients. One of the MAb-based options for HCL currently under clinical investigation involves recombinant immunotoxins, containing a fragment of a MAb and a bacterial toxin. The bacterial toxin, a highly potent fragment from Pseudomonas exotoxin, catalytically ADP-ribosylates elongation factor 2 (EF2), resulting in protein synthesis inhibition and apoptotic cell death. Recombinant immunotoxins tested in HCL patients include LMB-2, targeting CD25, and BL22, targeting CD22. An affinity matured version of BL22, termed moxetumomab pasudotox (formerly HA22 or CAT-8015) achieved high CR rates in phase I, and is currently undergoing multicenter Phase 3 testing. Phase I testing was without dose-limiting toxicity, although 2 patients had grade 2 hemolytic uremic syndrome (HUS) with transient grade 1 abnormalities in platelets and creatinine. Preclinical work is underway to identify residues on moxetumomab pasudotox leading to immunogenicity. Moxetumomab pasudotox is undergoing pivotal testing for relapsed and refractory HCL.


Hedgehog-driven myogenic tumors recapitulate skeletal muscle cellular heterogeneity.
Hedgehog (Hh) pathway activation in R26-SmoM2;CAGGS-CreER mice, which carry a tamoxifen-inducible activated Smoothened allele (SmoM2), results in numerous microscopic tumor foci in mouse skeletal muscle. These tumors exhibit a highly differentiated myogenic phenotype and resemble human fetal rhabdomyomas. This study sought to apply previously established strategies to isolate lineally distinct populations of normal mouse myofiber-associated cells in order to examine cellular heterogeneity in SmoM2 tumors. We demonstrate that established SmoM2 tumors are composed of cells expressing myogenic, adipocytic and hematopoietic lineage markers and differentiation capacity. SmoM2 tumors thus recapitulate the phenotypic and functional hetereogeneity observed in normal mouse skeletal muscle. SmoM2 tumors also contain an expanded population of PAX7+ and MyoD+ satellite-like cells with extremely low clonogenic activity. Selective activation of Hh signaling in freshly isolated muscle satellite cells enhanced terminal myogenic differentiation without stimulating proliferation. Our findings support the conclusion that SmoM2 tumors represent an aberrant skeletal muscle state and demonstrate that, similar to normal muscle, myogenic tumors contain functionally distinct cell subsets, including cells lacking myogenic differentiation potential.


Psychosocial aspects of athletic injuries as perceived by athletic trainers.
Despite the Psychosocial Strategies and Referral content area, athletic trainers (ATs) generally lack confidence in their ability to use this information. The current study's primary purpose was to determine (a) perceived psychological responses and coping behaviors athletes may present to ATs, (b) psychosocial strategies ATs currently use with their athletes, (c) psychosocial strategies ATs deem important to learn more about, and (d) ATs' current practices in referring athletes to counseling or sport psychology services. Mixed-methods study. Online survey containing both quantitative and qualitative items. A total of 215 ATs (86 male, 129 female), representing a response rate of 22.50%. The Athletic Training and Sport Psychology Questionnaire. Stress/anxiety (4.24 ± 0.82), anger (3.70 ± 0.96), and treatment adherence problems (3.62 ± 0.94) were rated as the primary psychological responses athletes may present upon injury. Adherence and having a positive attitude were identified as key determinants in defining athletes' successful coping with their injuries. The top 3 selected psychosocial strategies were keeping the athlete involved with the team (4.57 ± 0.73), using short-term goals (4.45 ± 0.67), and creating variety in rehabilitation exercises (4.32 ± 0.75). The top 3 rated psychosocial strategies ATs deem important to learn more about were understanding motivation (4.29 ± 0.89), using effective communication (4.24 ± 0.91), and setting realistic goals (4.22 ± 0.97). Of the sample, only 59 (27.44%) ATs reported referring an athlete for counseling services, and 37 (84.09%) of those who had access to a sport psychologist (n = 44) reported referring for sport psychology services. These results not only highlight ATs' current use of psychosocial strategies but also their desires to increase their current knowledge and understanding of these strategies while caring for injured athletes.


An approach to the management of children with problematic severe asthma.
Children with poor asthma control despite high levels of prescribed treatment are described as having problematic severe asthma. Most of these children have steroid sensitive disease which improves with adherence to daily inhaled corticosteroids and after having removed modifiable factors like poor inhalation technique, persistent adverse environmental exposures and psychosocial factors. These children are described as having "difficult-to-treat asthma" while children with persistent symptoms despite above-mentioned factors having been addressed are described as having "severe therapy-resistant asthma". In this review, we will describe the 6-step approach to the diagnosis and management of a child with problematic severe asthma adopted by The Royal Brompton Hospital (London, UK). The role of a multidisciplinary team is crucial for identification and treatment of modifiable factors and comorbidities in order to avoid invasive examinations and useless pharmacological treatments. The current knowledge on add-on therapies will be discussed.


Individual differences in false belief understanding are stable from 3 to 6 years of age and predict children's mental state talk with school friends.
Despite a wealth of studies in the field, longitudinal assessments of both the stability and predictive utility of individual differences in preschoolers' understanding of the mind remain scarce. To address these gaps, we applied latent variable analyses to (a) experimental data gathered from a socially diverse sample (N=101, 60 boys and 41 girls) at 3 and 6 years of age and (b) transcript-based coding of children's dyadic interactions with a best friend at age 6. Our results showed significant stability between latent factors of false belief understanding at ages 3 and 6 even with effects of verbal ability and inhibitory control controlled at both time points. In addition, false belief understanding at ages 3 and 6 showed both distal and proximal links with the frequency of children's talk about mental states at age 6 even when their overall talk and their friends' mental state talk were also controlled. We conclude that preschoolers' false belief understanding both directly and indirectly supports children's growing ability to discuss thoughts and feelings in their conversations with friends.


Localization of antigenic determinants in whole Drosophila embryos.
Procedures are described for removal of the vitelline membrane from gently fixed Drosophila embryos en masse. The resulting embryos retain excellent structural integrity and are now suitable for a variety of immunocytochemical and biochemical characterizations.


Performing scienceLove + Science David J. Glass In Vitro Productions, New York City Center, New York, NY, USA, 26 May to 6 July 2023.
A biologist captures the humanity of scientific research in a play about the AIDS crisis.


[Clinical evaluation on effects of functional muscular equal pressure zone on complete denture].
To study the clinical effect of the functional muscular equal pressure zone on complete denture. Artificial teeth were arranged within the functional muscular equal pressure zone. With this technique 35 complete dentures were made to rehabilitate 35 edentulous patients whose alveolar bones were moderately or seriously absorbed. After three months' following up, the satisfaction of these patients were investigate. After prosthesis treatment, 35 patients enunciated well and the aesthetic effect was favorable. 89 percent of these patients satisfied the retention and the stability of the maxillary denture, and 78 percent satisfied the retention and the stability of the mandibular denture. 79.5 percent of these patients satisfied the mastication efficiency. With the technique, the complete denture is fairly stable in patient's mouth. The technique can enhance the denture's retention and improve the patient's mastication efficiency, especially to these whose alveolar bones are moderately or seriously absorbed. Clinically the technique is of high practical value to these edentulous patients who are difficult to be rehabilitated.


Dispersal capacity and seed production in anemochorous plants.
Salisbury has argued that anemochory is less efficient than zoochory. His evidence indicates that zoochores produce fewer seeds and that far dispersing anemochores produce more seeds than do near dispersing anemochores. Limiting our discussion to the anemochore's part of the hypothesis, we reformulate Salisbury's measure of dispersal capacity into a more correct aerodynamic measure. This more correct equation does not support the relationship of increasing seed number per individual in further dispersing anemochores.


Fetal-neonatal passive immunization against Hemophilus influenzae, type b.
Twenty-one pregnant women were vaccinated with the polyribophosphate capsular antigen of Hemophilus influenzae, type b, at 34 to 36 weeks of gestation. All women experienced a large boost in their own antibody levels of anti-polyribophosphate capsular antigen, and 30% was transferred to their newborn infants. The newborn serum anti-polyribophosphate capsular antigen level at birth was 100-fold greater than that of control newborn infants, and the antibody persisted at a protective level for 12 months. Since newborn infants lose significant antibody by 3 months of age, they are susceptible to infection by Hemophilus influenzae, type b, such that it is the leading cause of meningitis in infants. The passive levels of anti-polyribophosphate capsular antigen achieved in these fetuses-neonates by active immunization of their mothers should theoretically lead to less disease caused by Hemophilus influenzae, type b, during infancy.


Comparison of three automated compounding devices for parenteral nutrition according to four key technical tests.
Automation of parenteral nutrition (PN) preparation is nowadays a recommended practice in order to reduce human errors and thus improve the safety and accuracy of the finished product. Other benefits of automation may include full documentation of preparation and a reduction in personnel requirements or staff injuries. The market of automation compounding presents different automated compounding devices (ACDs). The aim of this study is to compare the technical characteristics of ACDs by carrying out four specific challenges. Three ACDs: Two piston pumps with ACD 1: MediMix Multi 4120R (Impromediform) and ACD 2: Mibmix Compounder C12 (Hemedis), and one peristaltic pump ACD 3: ExactaMix Compounder EM2400 (Baxter) were assessed in a pharmaceutical manufacturing unit within a controlled atmosphere area, under horizontal laminar flow hood (LFH) according to four tests: volumetric accuracy, flush volume, smoke test, and a production test with three configurations of PN bags. For this test, a PN bag was considered accepted when all quality controls (weight, molar concentration of sodium, potassium and calcium) were fulfilled. The maximum relative biases found for the different ACDs were heterogeneous. ACD 1 had the best volumetric accuracy with respect to supplier specifications and for extreme volumes (0.2 mL). Evaluation of the flushing volume allowed the validation of 50 mL volumes for ACD 1 and ACD 3. The smoke test was only conclusive for ACD 1 under a horizontal LFH. The percentage of PN bags accepted were 98.8% for ACD 1, 70% for ACD 2%, and 95.5% for ACD 3. This study compared three ACDs according to four relevant and specific tests. Based on the data acquired, we conclude that ACD 1 is the most accurate, has the lowest flushing volume, is suitable for use in a LFH, and achieves the best results in the production test.


Feasibility of quality of life assessment in patients with upper gastrointestinal tract cancer.
Quality of life (QOL) is an important outcome after treatment for upper gastrointestinal tract cancer but few studies report good accrual and subsequent attrition is usually high. This study investigated the feasibility of a nurse-led service to obtain longitudinal QOL assessments and explored how clinical and sociodemographic factors influence patients' need for help to complete questionnaires. Fully informed patients were invited into the study. Baseline hospital assessments were scheduled by telephone and thereafter by post unless patients' health indicated the need for a home visit. In all, 128 out of 140 (91%) baseline QOL assessments were performed. Follow-up questionnaire completion was good, with 114 patients (89%) completing all but one of the expected assessments. At baseline, 41 (32%) patients required a lot of help to complete questionnaires. Patients requiring help were more likely to be undergoing palliative treatment than treatment aimed at cure (68 vs 33%; odds ratio 3.48, P<0.01). Patients' with advanced stage cancer of the upper gastrointestinal tract receiving palliative treatment require dedicated staff to ensure good compliance with longitudinal QOL data collection. It is essential to budget for this in clinical trails.


Protocol for a randomised clinical trial of transoral ultrasound versus standard of care in the diagnosis of peritonsillar abscess.
Peritonsillar infection is a common complication to acute tonsillitis in younger adults. If peritonsillar cellulitis progresses to a peritonsillar abscess (PTA), the primary treatment is surgical drainage. But distinguishing cellulitis from PTA on a standard clinical examination is difficult. This trial aims to explore whether point-of-care transoral ultrasound can improve diagnostic accuracy and guide successful needle aspiration in patients referred with PTA. A randomised, controlled multicentre trial will be conducted at the departments of otorhinolaryngology, head and neck surgery at Rigshospitalet and Odense University Hospital. Patients referred with PTA will be randomised to either standard clinical examination (control) or standard clinical examination with supplemental transoral ultrasound (intervention). The diagnostic accuracy, the total number of performed needle aspirations and the proportion of successful needle aspirations will be compared between the two groups. The difference will be evaluated using binary logistic regression and a generalised estimating equation to adjust for clustering of data within each physician and each hospital. A total of 88 patients are necessary to measure the clinical effect of adding transoral ultrasound. This study will explore the clinical benefits of adding transoral ultrasound to the diagnostic work-up of patients with peritonsillar infections. The Rigshospitalet and Odense University Hospital Foundation. Clinicaltrials NCT03824288.


Clinical characteristics and outcome of genitourinary tuberculosis in Sri Lanka: an observational study.
Although genitourinary Tuberculosis (GUTB) is the second commonest source of extrapulmonary TB in most countries, the reported rate of GUTB in Sri Lanka remains low. The characteristics of GUTB in Sri Lanka have not been studied and documented so far. We aimed to study the clinical and imaging characteristics, treatment modalities and outcome of GUTB in Sri Lanka. Data collected from patients treated by a single urological surgeon in two institutes consecutively over a period of 21 years were analysed. All patients with a microbiological and/or histopathological diagnosis of GUTB were included. Median duration of follow-up was 24 months (range: 6-96). There were 82 patients and 45 (54.9%) were men. The median age was 51 (range: 26-75) years. Most patients (39%, n = 32) had vague non-specific symptoms at presentation. Common specific symptoms at presentation were haematuria (15.8%, n = 13) and scrotal manifestations (15.8%, n = 13). Mantoux test was done in 70 patients and was > 10 mm in 62 (88.5%). Erythrocyte sedimentation rate was available in 69 patients and was > 30 mm in 54 (78.3%) patients. Chest x-ray and x-ray kidney-ureter-bladder (KUB) abnormalities were detected in 9 (11%) and 6 (7.3%) respectively. CT-urography was performed in 72 patients and abnormalities were detected in 57 (79%) patients. Forty-two patients underwent cystoscopy and 73.8% (n = 31) had abnormal findings. Microbiological diagnosis was feasible in 43 (52.4%) and rest were diagnosed histopathologically. Commonest organs involved were kidney (64.6%, n = 53), ureter (51.2%, n = 42), bladder (43.9%, n = 36) and testis/epididymis (15.8%, n = 13). One patient had TB of the prostate. All were treated primarily with anti-TB drugs however, 50 (61%) required ancillary therapeutic interventions. The majority of interventions were reconstructive surgeries (n = 20, 24.4%) followed by excisional surgeries (n = 19, 23.2%) and drainage procedures (n = 11, 13.4%). Seven patients developed serious adverse reactions to anti-TB drugs. Five patients developed a thimble bladder with disabling storage symptoms. Eight patients had deranged renal functions at diagnosis and three patients developed progressive deterioration of renal function and two patients died of end stage renal disease. The combination of urine for acid-fast bacilli, Mantoux test, CT-Urography, cystoscopy and histopathology is necessary to diagnose GUTB in resource-poor settings. Most ureteric strictures, non-functioning kidneys and epididymal masses need surgical treatment. Long-term follow up is essential to detect progressive deterioration of renal function.


[Essential aspects for the administration of blood components in hospitalized patients: A narrative literature review].
Transfusion medicine develops and disseminates guidelines that govern the optimal conditions for transfusion. The purpose of this article is to review the current evidence on the use of blood components. We searched PubMed, Scholar Google, ScienceDirect, SciELO and Cochrane web portals, as well as official documents published in the Chilean Society of Hematology. Articles from the last ten years were included, of which 42 were appropriate for this narrative literature review. First of all, there is a controversy between two types of strategies regarding the practice of red blood cell transfusion: a liberal strategy and a restrictive strategy. Second, for the management of coagulopathies, clotting times do not reflect the true ability of patients to clot. Third, to reverse the effect of coumadin, the administration of vitamin K would suffice over the use of fresh frozen plasma. Fourth, the use of physiological triggers could help define the best time for a transfusion.


Integrative role of neuropeptides and cytokines in cancer anorexia-cachexia syndrome.
The cachexia anorexia syndrome is a complex metabolic syndrome associated with cancer and some other palliative conditions characterized by involuntary weight loss involving fat and muscle, weight loss, anorexia, early satiety, fatigue, weakness due to shifts in metabolism caused by tumour by-products and cytokines. Various neuropeptides like Leptin, neuropeptide Y, melanocortin, agouti-related peptides have been known to regulate appetite and body weight. A comprehensive literature search was carried out on the websites of Pubmed Central (http://www.pubmedcentral.nih.gov/), National Library of Medicine (http://www.ncbl.nlm.nih.gov) and various other net resources. Data from observational studies shows that various cytokines (TNF-α, IL-6 and IL-1) are associated with metabolic changes resulting in cachexia in cancer patients. These cytokines may mimic the action of various neuropeptides resulting in anorexia, various metabolic effects resulting from enhanced catabolic state and weight loss. There is a need to understand and explore the role of various neuropeptides and cytokines in the pathophysiology of cancer-anorexia syndrome so that therapeutic measures may be designed for effective palliative care.


The Impact of a Multi-Pronged Intervention on Students' Perceptions of School Lunch Quality and Convenience and Self-Reported Fruit and Vegetable Consumption.
School lunch programs provide an opportunity to improve students' diets. We sought to determine the impact of a multifaceted intervention (cafeteria redesigns, increased points-of-sale and teacher education) on secondary students' perceptions of school-lunch quality and convenience and fruit and vegetable intake. Surveys (n = 12,827) from middle and high school students in 12 intervention and 11 control schools were analyzed. We investigated change in school-lunch perceptions and lunchtime and daily fruit and vegetable consumption from 2016 to 2018. Among 8th graders, perceptions that school lunch tastes good and that school lunch was enough to make students feel full increased 0.2 points (on a 5-point scale; p < 0.01) in intervention schools relative to control schools. Among 10th graders, lunchtime fruit and vegetable consumption increased 6% in intervention relative to control schools (p < 0.05 and p < 0.01 respectively). Daily fruit intake increased 0.1 cups/day in intervention relative to control schools among 9th graders (p < 0.01). This study provides important evidence on the limited effect of design approaches in the absence of meal changes. We observed only modest changes in school lunch perceptions and fruit and vegetable consumption that were not consistent across grades, suggesting that additional efforts are needed to improve school-lunch uptake.


Low back pain and lumbar radiculopathy as harbingers of acute myeloid leukemia recurrence in a patient with myeloid sarcoma.
Myeloid sarcoma (MS) is an extra-osseous, solid collection of myeloblasts. It is associated with myeloid leukemias, and rarely affects the spine. The most common clinical presentation of MS in spine patients is some form of pain related to compression of neural elements. Given that MS is rare, and its imaging characteristics are similar to other more common diagnoses, it is frequently missed on initial presentation. We present a 28-year-old female, in her fifth year of remission from AML, with low back pain and right lumbar radiculopathy. Initially, the leading diagnosis was schwannoma in preference to neurofibroma; however, intra-operative pathology and subsequent bone marrow biopsy revealed the tumor to be MS. This report highlights the difficulties of diagnosis of MS in patients in remission from acute myeloid leukemia. Thus, in patients with a history of leukemia, MS should be considered in the differential diagnosis of any epidural or nerve root tumor. Timely diagnosis and treatment are key to optimal outcomes.


Pathology Consultation on Patients With a Large Rh Immune Globulin Dose Requirement.
To review the differential diagnosis and laboratory issues for women with a large calculated dose of Rh immune globulin (RhIG). A case-based approach is used to review the differential diagnosis of patients with a large calculated dose of RhIG, RhIG dosing for women with baseline elevations in hemoglobin F, the formulations of RhIG, and issues for the transfusion medicine service with the release of large doses of RhIG. A large fetomaternal bleed after delivery requiring multiple doses of RhIG is rare. Such patients may require intravenous RhIG to avoid multiple injections. Patients with a large percentage of circulating fetal RBCs should be evaluated for a disorder of hemoglobin synthesis and, if present, should have quantification of the circulating fetal RBCs by flow cytometry. Accurate laboratory evaluation of women with large fetomaternal bleeds is essential for appropriate RhIG administration.


Calcium Salt of N-(5-Hydroxynicotinoyl)-L-Glutamic Acid Weakens Depressive-Like Behavior and Parkinsonian Syndrome in Experiment on Rodents.
We studied antidepressant and antiparkinsonian properties of N-(5-hydroxynicotinoyl)-Lglutamic acid calcium salt (Ampasse) in rodents. It was found that Ampasse in a dose of 30 mg/kg exhibited antidepressant activity in the forced swimming test in mice and in a dose of 0.1 mg/kg maximally alleviates the symptoms of parkinsonian syndrome induced by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57Bl/6 mice, and haloperidol-induced catalepsy in rats.


Nonmedical Prescription Drug Use among Adolescents: Global Epidemiological Evidence for Prevention, Assessment, Diagnosis, and Treatment.
This paper reviews the most recent epidemiological evidence on adolescent NMPD use. Particular attention is given to prevention, assessment and diagnosis of disorder, and treatment. While international in scope, global evidence is only available for NMPD use, morbidity and mortality estimates. Prevention strategies, assessment and treatment are U.S.-centric. The literature on prevention strategies lacks high-quality evidence. Assessment, diagnosis and treatment of NMPD use disorder have more robust evidence bases. Despite this, screening for NMPD (and other drug) use disorders is infrequent and insensitive, leading to incomplete treatment provision. Treatments are shown to be safe and effective, but disparities in provision prevent wide-scale amelioration of the adolescent NMPD use problem. Mental health care professionals and primary care physicians with adolescent patient populations should become involved in preventative strategies mentioned in this review. Additionally, higher screening rates will lead to less downstream problems related to NMPD use.


Total elbow arthroplasty for the treatment of distal humeral fractures.
To report the clinical-functional outcomes of the treatment of humeral distal fractures with a total elbow prosthesis. This retrospective study was performed in two surgical centres. A total of 23patients were included, with a mean age of 79years, and of which 21 were women. The inclusion criteria were: patients with humeral distal fractures, operated on using a Coonrad-Morrey prosthesis, and with a follow-up of more than one year. According to AO classification, 15fractures were type C3, 7 C2 and 1 A2. All patients were operated on without de-insertion of the extensor mechanism. The mean follow-up was 40 months. Flexor-extension was 123-17°, with a total mobility arc of 106° (80% of the contralateral side). Pain, according to a visual analogue scale was 1. The Mayo Elbow Performance Index (MEPI) was 83 points. Excellent results were obtained in 8 patients, good in 13, medium in 1, and poor in 1. The mean DASH (disability) score was 24 points. Treatment of humeral distal fractures with total elbow arthroplasty could be a good treatment option, but indications must be limited to patients with complex fractures, poor bone quality, with osteoporosis and low functional demands. In younger patients, the use is limited to serious cases where there is no other treatment option. Level of Evidence IV.


The peripheral cannabinoid receptor knockout mice: an update.
This review gives an overview of the CB2 receptor (CB2R) knockout (CB2R-/-) mice phenotype and the work that has been carried out using this mutant mouse. Using the CB2R-/- mice, investigators have discovered the involvement of CB2R on immune cell function and development, infection, embryonic development, bone loss, liver disorders, pain, autoimmune inflammation, allergic dermatitis, atherosclerosis, apoptosis and chemotaxis. Using the CB2R-/- mice, investigators have also found that this receptor is not involved in cannabinoid-induced hypotension. In addition, the CB2R-/- mice have been used to determine specific tissue CB2R expression. The specificity of synthetic cannabinoid agonists, antagonists and anti-CB2R antibodies has been screened using tissues from CB2R-/- mice. Thus, the use of this mouse model has greatly helped reveal the diverse events involving the CB2R, and has aided in drug and antibody screening.


[Pattern of lymph node metastasis and extent of lymphadenectomy for distal gastric cancer].
To analyze lymph node (LN) metastasis patterns and determine the appropriate extent of LN dissection in distal-third gastric cancer. Clinical data of 545 patients with distal third gastric cancer undergoing radical operation in the Fujian Provincial Hospital between 2001 and 2010 were analyzed retrospectively. The metastasis rate for each LN station was analyzed stratified by the depth of tumor invasion. The incidence of LN metastasis in this cohort was 38.2% (208/545). LN metastasis rate in mucosal cancer was 2.0% (2/99) and involved LNs were limited to station 1 LN stations. LN metastasis rate in submucosal cancer was 18.9% (18/95), significantly higher than that in mucosal cancer (P<0.01). The metastasis rates to groups No.7, 8 and 9 in station 2 were 5.3% (5/94), 3.2% (3/94), and 1.1% (1/89) respectively. In addition, 3 cases (3.2%) had metastasis in station 2 outside the range of groups 7, 8 and 9 including groups No.1, 11p and 12. Gastric cancer invading the muscularis propria or deeper layers showed an significant increased rate of metastasis (P<0.01). D1 dissection seems to be sufficient for mucosal cancer. Standard D2 dissection should be performed for cancers of the muscularis propria or deeper. For submucosal cancer, an extended D1+ dissection is required for complete removal of metastatic nodes.


IgG1 conformational behavior: elucidation of the N-glycosylation role via molecular dynamics.
Currently, monoclonal antibodies (mAbs) are the most used biopharmaceuticals for human therapy. One of the key aspects in their development is the control of effector functions mediated by the interaction between fragment crystallizable (Fc) and Fcγ receptors, which is a secondary mechanism of the action of biotherapeutics. N-glycosylation at the Fc portion can regulate these mechanisms, and much experimental evidence suggests that modifications of glycosidic chains can affect antibody binding to FcγRIIIa, consequently impacting the immune response. In this work, we try to elucidate via in silico procedures the structural role exhibited by glycans, particularly fucose, in mAb conformational freedom that can potentially affect the receptor recognition. By using adalimumab, a marketed IgG1, as a general template, after rebuilding its three-dimensional (3D) structure through homology modeling approaches, we carried out molecular dynamics simulations of three differently glycosylated species: aglycosylated, afucosylated, and fucosylated antibody. Trajectory analysis showed different dynamical behaviors and pointed out that sugars can influence the overall 3D structure of the antibody. As a result, we propose a putative structural mechanism by which the presence of fucose introduces conformational constraints in the whole antibody and not only in the Fc domain, preventing a conformation suitable for the interaction with the receptor. As secondary evidence, we observed a high flexibility of the antibodies that is translated into an asymmetric behavior of Fab portions shown by all the simulated biopolymers, making the dynamical asymmetry a new, to our knowledge, molecular aspect that may be further investigated. In conclusion, these findings can help understand the contribution of sugars on the structural architecture of mAbs, paving the way to novel strategies of pharmaceutical development.


Computer program for evaluation, physicochemical characterization and optimization of competitive protein binding assays: comparison of four curve-fitting models in peptide and steroid radioimmunoassays.
A modular construced computer program for evaluation, physicochemical characterization and optimization of compititive protein binding assays is put forward. The program allows standard curve fitting by the following models: spline approximation, semi-logarithmic interpolation, logit-log regression and logit-log interpolation. The suitability of these models was studied in a series of routine steroid radioimmunoassays (deoxycorticosterone, deoxycortisol, cortisol and aldosterone) and peptide radioimmunoassays (angiotensin I and angiotensin II). The spline approximation model was used as an approximate reference model. In all assays the logit-log interpolation model exhibited the best correlation with the spline approximation model. In the steroid assays the logit-log regression model was found to be inferior to the other models; in the peptide assays it was equal to or superior to the semi-logarithmic interpolation model. The study on the physicochemical parameters of the antigen-antibody reactions demonstrated that affinity of steroid antibodies was much lower than that of the peptide antibodies. Consequently the degree of antibody saturation at zero dose in the routine peptide assays was greater than 50% and in the routine steroid assays was less than 50%. The relationship of assay characteristics to the applicability of particular curve-fitting models is discussed.


Vascularised iliac graft as a method of acetabular augmentation in subluxed hip in adolescents.
This article presents the clinical experience of patients with a dysplasic subluxated hip treated with the same procedure involving a vascularised graft of iliac crest by sartorius muscle. This study was performed in three different centres, in two different countries, and in 31 patients with 37 hips (9 bilateral). All patients were clinically evaluated according to the Merle d Aubigne scale and radiological measuring of acetabular coverage, Sharp angle, and CE angle. Walking ability preoperatively was 4.87 and postoperatively 5.12, which was not statistically significant. Preoperative inclination acetabular angle was 59.0 degrees +/- 6.23 and postoperatively 37.5 degrees +/- 6.08 (P < 0.00001). Preoperative CE angle was -2.03 degrees +/- 13.5 and postoperatively was 41.0 degrees +/- 12.3 ( P < 0.00001). Index head acetabulum had a preoperative coverage of 48.3% +/- 13.0 and postoperatively 100.8% +/- 19.5. The head sphericity did not show any statistically significant difference in relation to the results. The results obtained were satisfactory from every point of view, making this the procedure of choice in the armamentarium to delay the need for a total joint as treatment of early osteoarthritis in young adults.


Correlates of health-related quality of life in youth with psychogenic non-epileptic seizures.
Few studies have examined factors associated with health-related quality of life (HRQoL) in youth with psychogenic non-epileptic seizures (PNES). In adults, internalizing symptoms such as depression have been shown to be more closely associated with HRQoL than seizure frequency, however, this has not been studied in samples of youth. Investigations into these areas are needed in order to enhance our understanding of the impact of this condition on children and adolescents and inform future clinical intervention. The current study includes 37 youth and one of their parents who attended a clinic visit for treatment of PNES. Children and parents completed measures of psychological functioning, and medical data were extracted from patient charts. Parent-reported anxiety (B=-0.45, p = 0.05) and depression (B=-0.60, p = 0.01) were related to parent-report of HRQoL; self-report of depression was related to self-reported HRQoL (B=-0.90, p < 0.001). Seizure frequency, somatic complaints, and social problems were not related to HRQoL in this sample. Internalizing symptoms, not seizure frequency, are associated with poorer overall functioning in youth with PNES. Interventions focused on improving anxiety and depression in addition to seizure cessation may contribute to improved HRQoL in youth with PNES more so than those focused on seizure cessation alone.


Development and Use of a Calculator to Measure Pediatric Low-Value Care Delivered in US Children's Hospitals.
The scope of low-value care in children's hospitals is poorly understood. To develop and apply a calculator of hospital-based pediatric low-value care to estimate prevalence and cost of low-value services. This cross-sectional study developed and applied a calculator of hospital-based pediatric low-value care to estimate the prevalence and cost of low-value services among 1 011 950 encounters reported in 49 US children's hospitals contributing to the Pediatric Health Information System (PHIS) database. To develop the calculator, a multidisciplinary stakeholder group searched existing pediatric low-value care measures and used an iterative process to identify and operationalize relevant hospital-based measures in the PHIS database. Children with an eligible encounter in 2019 were included in the calculator-applied analysis. Two cohorts were analyzed: an emergency department cohort (with encounters resulting in emergency department discharge) and a hospitalized cohort. Eligible condition-specific hospital encounters. The proportion and volume of encounters in which low-value services were delivered and their associated standardized costs. Measures were ranked by those outcomes. There were 1 011 950 encounters eligible for 1 or more of 30 calculator-included measures in 2019; encounters were incurred by 816 098 unique patients with a median age of 3 years (IQR, 1-8 years). In the emergency department cohort, low-value services delivered in the greatest percentage of encounters were Group A streptococcal testing among children younger than 3 years with pharyngitis (3679 of 9785 [37.6%]), computed tomography scan for minor head injury (7541 of 42 602 [17.7%]), and bronchodilators for treatment of bronchiolitis (8899 of 55 616 [16.0%]). In the hospitalized cohort, low-value care was most prevalent for broad-spectrum antibiotics in the treatment of community-acquired pneumonia (3406 of 5658 [60.2%]), acid suppression therapy for infants with esophageal reflux (3814 of 7507 of [50.8%]), and blood cultures for uncomplicated community-acquired pneumonia (2277 of 5823 [39.1%]). Measured low-value services generated nearly $17 million in total standardized cost. The costliest services in the emergency department cohort were computed tomography scan for abdominal pain (approximately $1.8 million) and minor head injury (approximately $1.5 million) and chest radiography for asthma (approximately $1.1 million). The costliest services in the hospitalized cohort were receipt of 2 or more concurrent antipsychotics (approximately $2.4 million), and chest radiography for bronchiolitis ($801 680) and asthma ($625 866). This cross-sectional analysis found that low-value care for some pediatric services was prevalent and costly. Measuring receipt of low-value services across conditions informs prioritization of deimplementation efforts. Continued use of this calculator may establish trends in low-value care delivery.


Occlusal caries diagnosis: a changing challenge for clinicians and epidemiologists.
The diagnosis of occlusal caries is an integral part of an epidemiologist's task, whether carrying out cross-sectional national caries prevalence surveys to assist with planning and the evaluation of service provision, or clinical trials of caries preventive agents. Similarly, the clinician also carries out this same overall diagnostic procedure in order to plan care for individual patients, although he/she will usually have access to improved facilities and diagnostic aids. This paper reviews the different problems now being encountered by both epidemiologists and clinicians in the face of changes in the presentation of the disease at this site and the qualifications which should now be appreciated when extrapolating from the results of surveys employing comparatively gross criteria. It explores recent developments in diagnostic aids and makes suggestions as to how further information might be obtained in future which would aid the valid comparison of diagnoses made by these two groups of dentists.


Fate of N-nitrosodimethylamine, trihalomethane and haloacetic acid precursors in tertiary treatment including biofiltration.
The presence of disinfection by-products (DBPs) such as trihalomethanes (THMs), haloacetic acids (HAAs) and N-nitrosamines in water is of great concern due to their adverse effects on human health. In this work, the removal of N-nitrosodimethylamine (NDMA), total THM and five HAA precursors from secondary effluent by biological activated carbon (BAC) is investigated at full and pilot scale. In the pilot plant two filter media, sand and granular activated carbon, are tested. In addition, we evaluate the influence of ozonation prior to BAC filtration on its performance. Among the bulk of NDMA precursors, the fate of four pharmaceuticals containing a dimethylamino moiety in the chemical structure are individually investigated. Both NDMA formation potential and each of the studied pharmaceuticals are dramatically reduced by the BAC even in the absence of main ozonation prior to the filtration. The low removal of NDMA precursors at the sand filtration in comparison to the removal of NDMA precursors at the BAC suggests that adsorption may play an important role on the removal of NDMA precursors by BAC. Contrary, the precursors for THM and HAA formation are reduced in both sand filtration and BAC indicating that the precursors for the formation of these DBPs are to some extent biodegradable.


Imaging the infected heart.
This Focus discusses the merits of modern imaging techniques for the management of patients with suspected or proven infection and also addresses the challenges of detecting infective endocarditis early.


Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr.
The HIV-1 protein Vpr is critical for a number of viral functions including a unique ability to arrest T-cells at a G2/M checkpoint and induce subsequent apoptosis. It has been shown to interact specifically with the second UBA (ubiquitin associated) domain found in the DNA repair protein HHR23A, a highly evolutionarily conserved protein. This domain is a commonly occurring sequence motif in some members of the ubiquitination pathway, UV excision repair proteins, and certain protein kinases. The three dimensional structure of the UBA domain, determined by NMR spectroscopy, is presented. The protein domain forms a compact three-helix bundle. One side of the protein has a hydrophobic surface that is the most likely Vpr target site.


A functionalized UiO-66 MOF for turn-on fluorescence sensing of superoxide in water and efficient catalysis for Knoevenagel condensation.
In the present work, a new MOF material of the UiO-family called Zr-UiO-66-NH-CH2-Py (1) has been obtained by the solvothermal technique and successfully characterized. The MOF structure was assembled with 2-((pyridin-4-ylmethyl) amino) terephthalic acid (H2BDC-NH-CH2-Py) as linker and Zr4+ ion. The activated form of 1 (called 1') exhibits considerable thermal and chemical stability. Compound 1' showed a very rapid and selective response for the fluorometric sensing of superoxide (O2·-) in aqueous medium even in the presence of the potentially competitive reactive oxygen species (ROS). The limit of detection value for O2·- sensing is 0.21 μM, which is comparable with those of the reported O2·- sensors. This is the first MOF based fluorescent sensor for the detection of O2·-. The response time of this MOF sensor for O2·- is very short (240 s). On the other hand, 1' was employed as a solid heterogeneous catalyst for Knoevenagel condensation between benzaldehyde and ethyl cyanoacetate at 80 °C in ethanol resulting in a very high yield of the desired product. The effects of the esterified linker ((CH3)2BDC-NH-CH2-Py) and the corresponding metal salt (ZrCl4) on this catalytic reaction were examined separately. We have also tested the substrate scope elaborately for the catalytic reaction promoted by catalyst 1'.


Unity in diversity-food plants and fungi of Sakartvelo (Republic of Georgia), Caucasus.
The Republic of Georgia is part of the Caucasus biodiversity hotspot, and human agricultural plant use dates back at least 6000 years. Over the last years, lots of ethnobotanical research on the area has been published. In this paper, we analyze the use of food plants in the 80% of Georgia not occupied by Russian forces. We hypothesized that (1) given the long tradition of plant use, and the isolation under Soviet rule, plant use both based on home gardens and wild harvesting would be more pronounced in Georgia than in the wider region, (2) food plant use knowledge would be widely and equally spread in most of Georgia, (3) there would still be incidence of knowledge loss despite wide plant use, especially in climatically favored agricultural regions in Western and Eastern Georgia. From 2013 to 2019, we interviewed over 380 participants in all regions of Georgia not occupied by Russian forces and recorded over 19,800 mentions of food plants. All interviews were carried out in the participants' homes and gardens by native speakers of Georgian and its dialects (Imeretian, Rachian, Lechkhumian, Tush, Khevsurian, Psavian, Kakhetian), other Kartvelian languages (Megrelian, Svan) and minority languages (Ossetian, Ude, Azeri, Armenian, Greek). The regional division was based primarily on historic provinces of Georgia, which often coincides with the current administrative borders. The total number of taxa, mostly identified to species, including their varieties, was 527. Taxonomically, the difference between two food plant groups-garden versus wild-was strongly pronounced even at family level. The richness of plant families was 65 versus 97 families in garden versus wild plants, respectively, and the difference was highly significant. Other diversity indices also unequivocally pointed to considerably more diverse family composition of wild collected versus garden plants as the differences between all the tested diversity indices appeared to be highly significant. The wide use of leaves for herb pies and lactofermented is of particular interest. Some of the ingredients are toxic in larger quantities, and the participants pointed out that careful preparation was needed. The authors explicitly decided to not give any recipes, given that many of the species are widespread, and compound composition-and with it possible toxic effects-might vary across the distribution range, so that a preparation method that sufficiently reduces toxicity in the Caucasus might not necessary be applicable in other areas. Relationships among the regions in the case of wild food plants show a different and clearer pattern. Adjacent regions cluster together (Kvemo Zemo Racha, and Zemo Imereti; Samegrelo, Guria, Adjara, Lechkhumi and Kvemo and Zemo Svaneti; Meskheti, Javakheti, Kvemo Kartli; Mtianeti, Kakheti, Khevsureti, Tusheti. Like in the case of the garden food plants, species diversity of wild food plants mentioned varied strongly. Climate severity and traditions of the use of wild food plants might play role in this variation. Overall food plant knowledge is widely spread all-across Georgia, and broadly maintained.


Nuclear selenoproteins and genome maintenance.
Selenium is an essential metalloid required for the expression of selenoproteins. While cells are constantly challenged by clastogens of endogenous and exogenous origins, genome integrity is maintained by direct repair of DNA damage, redox balance, and epigenetic regulation. To date, only five selenoproteins are experimentally demonstrated to reside in nucleus, exclusively or partially, including selenoprotein H, methionine-R-sulfoxide reductase 1, glutathione peroxidase-4, thioredoxin reductase-1, and thioredoxin glutathione reductase. All these five selenoproteins have demonstrated or potential roles in redox regulation and genome maintenance. Selenoprotein H is known to transactivate the expression of a couple of genes against oxidative stress. The thioredoxin reductase-1b isoform delivers estrogen receptor-α and -β to the nucleus. Nuclear glutathione peroxidase-4 epigenetically and globally inhibits gene expression through the maintenance of chromatin compactness in testes. Continued studies on how these and additional nuclear selenoproteins regulate genome stability will have profound impact on advancing our understanding in selenium regulation of optimal health. © 2015 IUBMB Life, 68(1):5-12, 2016.