Depression and family arguments: disentangling reciprocal effects for women and men.
Depression is a debilitating condition that affects the individual and the family. This study sought to identify potential reciprocal influences between family arguments and depressive symptoms among clinically depressed patients over a 23-year span. The present study employed a longitudinal, observational design with 424 depressed patients. Separate cross-lagged path models examined longitudinal associations for women and men over 23 years while adjusting for age, income, and marital and parental status. Among depressed men, more severe baseline depressive symptoms predicted more family arguments 10 years later. Among depressed women, more severe baseline depressive symptoms predicted fewer family arguments 1 year later, while more severe depressive symptoms at 10-year follow-up predicted more family arguments at 23-year follow-up. More family arguments predicted more severe depressive symptoms among women and men, with some variation in the time intervals of these associations. These findings suggest that while depressive symptoms may temporarily diminish family arguments among women, such symptoms were associated with more family arguments over longer time intervals. Moreover, family arguments put depressed men and women at risk for more severe depressive symptoms. These results support the use of screening for family arguments and interventions to help depressed individuals develop skills to manage interpersonal conflict.


Disposition of a 14C-labeled bioerodible polyorthoester and its hydrolysis products, 4-hydroxybutyrate and cis,trans-1,4-bis(hydroxymethyl)cyclohexane, in rats.
Disposition of the 14C-labeled bioerodible polymer poly(2,2-dioxy-cis,trans-1,4-cyclohexane dimethylene tetrahydrofuran) (ALZAMER C101ct) and its ultimate hydrolysis products, 4-hydroxybutyrate (4HB) and cis,trans-1,4-bis(hydroxymethyl)cyclohexane (CHDM), was assessed in vivo in rats 24 hr after sc administration of the 14C-labeled polymer or hydrolysis products. The hydrolysis products were rapidly metabolized and eliminated, whether administered directly or via in vivo erosion of the polymer. At 24 hr, fractional distribution of carbon-14 derived from 4HB was 65 to 75% in expired CO2, 5 to 10% in urine, 1 to 2% in feces, and 15 to 19% in tissues. For CHDM, distribution was 92 to 96% in urine, 2 to 3% in feces, and 0.3 to 3% in tissues. Hydrolysis products or metabolites were not sequestered in specific tissues. Pretreatment with unlabeled polymer for 28 days had little effect on the disposition of carbon-14. Minor differences in disposition between the polymer and its hydrolysis products are discussed.


Modulator figure of merit for short reach data links.
The traditional Mach-Zehnder modulator (MZM) figure of merit (FOM) has been defined as (Vπ2)/υ3dBe, and works effectively for LiNbO3 long haul modulators. However, for plasma dispersion based electro-optic modulators, or any modulator that has an inherent relationship between its bandwidth, required drive voltage, and optical insertion loss/gain, this FOM is inappropriate. This is particularly true for short reach links with no optical amplification. In the following, we propose a new modulator FOM (M-FOM) based on device metrics that are essential for short-reach links, such as the peak-to-peak drive voltage, modulator rise-fall time, and relative optical modulation amplitude. Link sensitivity measurements from two MZMs that have different bandwidths and optical losses are compared using our M-FOM to demonstrate its utility. Furthermore, we present a novel application protocol of our M-FOM to provide deeper insight into the relative system impact that modulator performance has on data links with no optical amplification, by taking the ratio of M-FOMs from two modulators driven with the same radio frequency drive power.


Optimal resting-growth strategies of microbial populations in fluctuating environments.
Bacteria spend most of their lifetime in non-growing states which allow them to survive extended periods of stress and starvation. When environments improve, they must quickly resume growth to maximize their share of limited nutrients. Cells with higher stress resistance often survive longer stress durations at the cost of needing more time to resume growth, a strong disadvantage in competitive environments. Here we analyze the basis of optimal strategies that microorganisms can use to cope with this tradeoff. We explicitly show that the prototypical inverse relation between stress resistance and growth rate can explain much of the different types of behavior observed in stressed microbial populations. Using analytical mathematical methods, we determine the environmental parameters that decide whether cells should remain vegetative upon stress exposure, downregulate their metabolism to an intermediate optimum level, or become dormant. We find that cell-cell variability, or intercellular noise, is consistently beneficial in the presence of extreme environmental fluctuations, and that it provides an efficient population-level mechanism for adaption in a deteriorating environment. Our results reveal key novel aspects of responsive phenotype switching and its role as an adaptive strategy in changing environments.


Transmission of herpes simplex virus Type 2 among factory workers in Ethiopia.
The herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) epidemics are believed to fuel each other, especially in sub-Saharan countries. In Ethiopia during 1997-2002, a retrospective study was conducted to examine risk factors for infection and transmission of HSV-2, in a cohort of 1612 factory workers. Prevalence of HSV-2 seropositivity at enrollment was 40.9%, and incidence of seroconversion was 1.8 seroconversions/100 person-years (PY), which decreased over time. Independent risk factors for seropositivity were having an HSV-2-seropositive partner, female sex, HIV antibodies, positive Treponema pallidum particle agglutination assay result, older age, low education level, and orthodox religion. These same factors were independent risk factors for HSV-2 seroconversion, with the exception of the latter 3. Most HSV-2-infected persons did not report symptoms. Among 41 monogamous HSV-2-serodiscordant heterosexual couples, incidence of HSV-2 seroconversion was 20.75 seroconversions/100 PY for women and 4.93 seroconversions/100 PY for men. The high burden of both HSV-2 and HIV infection in Ethiopia warrants stringent control measures.


Crosstalk between fibroblast growth factor 23, iron, erythropoietin, and inflammation in kidney disease.
Recent research has revealed that regulation of the bone-secreted hormone fibroblast growth factor 23 (FGF23) is not limited to classical mineral factors. Specifically, bidirectional relationships have been described between FGF23 production and anemia, iron status, and inflammation. Here, we will review the latest published articles on the crosstalk between FGF23 and the aforementioned nonclassical factors. It has been recently reported that erythropoietin, iron deficiency, and inflammation increase FGF23 production and metabolism. Moreover, FGF23 promotes anemia and regulates inflammatory responses. These findings are particularly important in the setting of chronic kidney disease which is characterized by elevated FGF23 levels and several associated comorbidities. Regulation of FGF23 is complex and involves many bone and renal factors. More recently, erythropoietin, iron deficiency, and inflammation have been also shown to affect FGF23 transcription and cleavage. Importantly, FGF23 has emerged as a regulator of erythropoiesis, iron metabolism, and inflammation. These findings provide novel and important insights into the pathophysiologic mechanisms of chronic kidney disease and may present new opportunities for therapeutic clinical interventions.


The polarization of immune cells in the tumour environment by TGFbeta.
Transforming growth factor-beta (TGFbeta) is an immunosuppressive cytokine produced by tumour cells and immune cells that can polarize many components of the immune system. This Review covers the effects of TGFbeta on natural killer (NK) cells, dendritic cells, macrophages, neutrophils, CD8(+) and CD4(+) effector and regulatory T cells, and NKT cells in animal tumour models and in patients with cancer. Collectively, many recent studies favour the hypothesis that blocking TGFbeta-induced signalling in the tumour microenvironment enhances antitumour immunity and may be beneficial for cancer therapy. An overview of the current drugs and reagents available for inhibiting TGFbeta-induced signalling and their phase in clinical development is also provided.


Individual and patch behaviour in structured metapopulation models.
Density dependent Markov population processes with countably many types can often be well approximated over finite time intervals by the solution of the differential equations that describe their average drift, provided that the total population size is large. They also exhibit diffusive stochastic fluctuations on a smaller scale about this deterministic path. Here, it is shown that the individuals in such processes experience an almost deterministic environment. Small groups of individuals behave almost independently of one another, evolving as Markov jump processes, whose transition rates are prescribed functions of time. In the context of metapopulation models, we show that 'individuals' can represent either patches or the individuals that migrate among the patches; in host-parasite systems, they can represent both hosts and parasites.


Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal.
To report a case of alcohol withdrawal and delirium tremens successfully treated with adjunctive dexmedetomidine. A 30-year-old man with a history of alcohol abuse was admitted to the general medical unit because of altered mental status and agitation. He was initially treated for alcohol withdrawal with benzodiazepines; his condition then deteriorated and he was transferred to the intensive care unit. Because of the patient's poor response to benzodiazepines (oxazepam and lorazepam, with midazolam the last one used), intravenous dexmedetomidine was started at an initial dose of 0.2 microg/kg/h and titrated to 0.7 microg/kg/h to the patient's comfort. Midazolam was subsequently tapered to discontinuation due to excessive sedation. In the intensive care unit, the patient's symptoms remained controlled with use of dexmedetomidine alone. He remained in the intensive care unit for 40 hours; dexmedetomidine was then tapered to discontinuation and the patient was transferred back to the general medical unit on oral oxazepam and thiamine, which had been started in the emergency department. He was discharged after 5 days. A review of the PubMed database (1989-2007) failed to identify any other instances of dexmedetomidine having been used as the principal agent to treat alcohol withdrawal. The use of sedative to treat delirium tremens is well documented, with benzodiazepines being the agents of choice. The clinical utility of benzodiazepines is limited by their stimulation of the gamma-aminobutyric acid receptors, an effect not shared by dexmedetomidine, a central alpha(2)-receptor agonist that induces a state of cooperative sedation and does not suppress respiratory drive. In patients with delirium tremens, dexmedetomidine should be considered as an option for primary treatment. This case illustrates the need for further studies to investigate other potential uses for dexmedetomidine.


NF-kappaB-inducing kinase restores defective IkappaB kinase activity and NF-kappaB signaling in intestinal epithelial cells.
Cytokine-stimulated IkappaBalpha degradation is impaired in HT-29 and primary intestinal epithelial cells. To gain more insight into the mechanism of this defect, we dissected cytokine-induced NF-kappaB signaling pathway in HT-29 cells. IL-1beta and TNF, alone or in combination with IFNgamma, failed to induce IkappaBalpha or IkappaBbeta degradation in HT-29 cells. Despite similar 125I-IL-1beta binding, HT-29 cells displayed no IRAK degradation, a 75% reduction of IKK activity, and decreased IkappaBalpha phosphorylation, NF-kappaB DNA binding activity and IL-8 mRNA accumulation in response to IL-1beta compared to Caco-2 cells. Selective activation of NF-kappaB pathway by adenoviral delivery of NF-kappaB-inducing kinase (Ad5NIK) or IKKbeta (Ad5IKKbeta) strongly activated IKK activity (>20 fold) in HT-29 cells with concomitant endogenous IkappaBalpha serine 32 phosphorylation and total IkappaBalpha degradation. In addition, NF-kappaB DNA binding activity and IL-8 secretion is higher in Ad5NIK-infected than in IL-1beta-stimulated HT-29 cells. These data show that altered NF-kappaB signaling is associated with impaired stimulation of an upstream IKK activator.


The Brazilian founder mutation TP53 p.R337H is uncommon in Portuguese women diagnosed with breast cancer.
Since the first studies reporting the TP53 p.R337H mutation as founder mutation in Southern and Southeastern Brazil, there has been controversy on its origin. Preliminary analysis of a small subset of Brazilian mutation carriers revealed that the haplotype incided on a Caucasian background. The vast majority of carriers identified today reside in Brazil or, if identified in other countries, are Brazilian immigrants. To our knowledge, the only two exceptions of carriers without a recognizable link with Brazil are two European families, from Portugal and Germany. Haplotype analysis in the Portuguese family revealed the same haplotype identified in Brazilian individuals, but in the German family, a distinct haplotype was found. Knowing that a significant proportion of women with breast cancer (BC) in Southern Brazil are p.R337H carriers, we analyzed p.R337H in a Portuguese cohort of women diagnosed with this disease. Median age at diagnosis among the first 573 patients tested was 60 years and 100 (17.4%) patients had been diagnosed at or under the age of 45 years. Mutation screening failed to identify the mutation in the 573 patients tested. These results are in contrast with the mutation frequency observed in a study including 815 BC-affected women from Brazil, in which carrier frequencies of 12.1 and 5.1% in pre- and postmenopausal women were observed, respectively. These findings suggest that the Brazilian founder mutation p.R337H, the most frequent germline TP53 mutation reported to date, is not a common germline alteration in Portuguese women diagnosed with BC.


GC-MS/MS analysis for source identification of emerging POPs in PM2.5.
Emerging POPs have received increasing attention due to their potential persistence and toxicity, but thus far the report regarding the occurrence and distribution of these POPs in PM2.5 is limited. In this study, an extremely sensitive and reliable method, using ultrasonic solvent extraction and silica gel purification followed by gas chromatography coupled with electron ionization triple quadrupole mass spectrometry, was developed and used for the trace analysis of hexachlorobutadiene (HCBD), pentachloroanisole (PCA) and its analogs chlorobenzenes (CBs) in PM2.5 from Taiyuan within a whole year. The limits of detection and limits of quantitation of analytes were 1.14 × 10-4‒2.74 × 10-4 pg m-3 and 3.80 × 10-4‒9.14 × 10-4 pg m-3. HCBD and PCA were detected at the mean concentrations of 3.69 and 1.84 pg m-3 in PM2.5, which is reported for the first time. Based on the results of statistical analysis, HCBD may come from the unintentional emission of manufacture or incineration of chlorinate-contained products but not coal combustion, while O3-induced photoreaction was the potential source of PCA in PM2.5. The temporal distributions of CBs in PM2.5 were closely related to coal-driven or agricultural activities. Accordingly, our study reveals the contamination profiles of emerging POPs in PM2.5 from Taiyuan.


Increasing physical activity in stroke survivors using STARFISH, an interactive mobile phone application: a pilot study.
Following stroke, people are generally less active and more sedentary which can worsen outcomes. Mobile phone applications (apps) can support change in health behaviors. We developed STARFISH, a mobile phone app-based intervention, which incorporates evidence-based behavior change techniques (feedback, self-monitoring and social support), in which users' physical activity is visualized by fish swimming. To evaluate the potential effectiveness of STARFISH in stroke survivors. Twenty-three people with stroke (12 women; age: 56.0 ± 10.0 years, time since stroke: 4.2 ± 4.0 years) from support groups in Glasgow completed the study. Participants were sequentially allocated in a 2:1 ratio to intervention (n = 15) or control (n = 8) groups. The intervention group followed the STARFISH program for six weeks; the control group received usual care. Outcome measures included physical activity, sedentary time, heart rate, blood pressure, body mass index, Fatigue Severity Scale, Instrumental Activity of Daily Living Scale, Ten-Meter Walk Test, Stroke Specific Quality of Life Scale, and Psychological General Well-Being Index. The average daily step count increased by 39.3% (4158 to 5791 steps/day) in the intervention group and reduced by 20.2% (3694 to 2947 steps/day) in the control group (p = 0.005 for group-time interaction). Similar patterns of data and group-time interaction were seen for walking time (p = 0.002) and fatigue (p = 0.003). There were no significant group-time interactions for other outcome measures. Use of STARFISH has the potential to improve physical activity and health outcomes in people after stroke and longer term intervention trials are warranted.


Molecular Characterizations of the er1 Alleles Conferring Resistance to Erysiphe pisi in Three Chinese Pea (Pisum sativum L.) Landraces.
Powdery mildew caused by Erysiphe pisi DC. is a major disease affecting pea worldwide. This study aimed to confirm the resistance genes contained in three powdery mildew-resistant Chinese pea landraces (Suoshadabaiwan, Dabaiwandou, and Guiwan 1) and to develop the functional markers of the novel resistance genes. The resistance genes were identified by genetic mapping and PsMLO1 gene sequence identification. To confirm the inheritance of powdery mildew resistance in the three Landraces, the susceptible cultivars Bawan 6, Longwan 1, and Chengwan 8 were crossed with Suoshadabaiwan, Dabaiwandou, and Guiwan 1 to produce F1, F2, and F2:3 populations, respectively. All F1 plants were susceptible to E. pisi, and phenotypic segregation patterns in all the F2 and F2:3 populations fit the 3:1 (susceptible: resistant) and 1:2:1 (susceptible homozygotes: heterozygotes: resistant homozygotes) ratios, respectively, indicating powdery mildew resistance in the three Landraces were controlled by a single recessive gene, respectively. The analysis of er1-linked markers and genetic mapping in the F2 populations suggested that the recessive resistance genes in three landraces could be er1 alleles. The cDNA sequences of 10 homologous PsMLO1 cDNA clones from the contrasting parents were obtained. A known er1 allele, er1-4, was identified in Suoshadabaiwan. Two novel er1 alleles were identified in Dabaiwandou and Guiwan 1, which were designated as er1-13 and er1-14, respectively. Both novel alleles were characterized with a 1-bp deletion (T) in positions 32 (exon 1) and 277 (exon 3), respectively, which caused a frame-shift mutation to result in premature termination of translation of PsMLO1 protein. The co-dominant functional markers specific for er1-13 and er1-14, KASPar-er1-13, and KASPar-er1-14 were developed and effectively validated in populations and pea germplasms. Here, two novel er1 alleles were characterized and their functional markers were validated. These results provide powerful tools for marker-assisted selection in pea breeding.


Turnover of a prostaglandin precursor, arachidonic acid, in rheumatoid arthritis.
The plasma concentration and the turnover of free arachidonic and oleic acids were determined in patients with rheumatoid arthritis and in control subjects. The plasma level of free arachidonic acid, but not of oleic acid, was significantly decreased in male rheumatoid patients. Female patients did not differ from healthy subjects in this respect. Following treatment with indomethacin, a significant increase in the plasma concentration of free arachidonic acid was observed in rheumatoid patients of both sexes. It is suggested that the findings in the rheumatoid patients reflect a partial exhaustion of the pool of arachidonic acid serving as precursor in the synthesis of prostaglandin.


Monitoring cytomegalovirus IE-1 and pp65-specific CD4+ and CD8+ T-cell responses after allogeneic stem cell transplantation may identify patients at risk for recurrent CMV reactivations.
We studied the recovery of CMV-specific CD4+ and CD8+ T-cell immunity in 52 recipients of allogeneic stem cell transplantation (SCT). The proportions of IFN-gamma-producing CD4+ and CD8+ T cells upon in vitro activation using peptide pools representing the CMV pp65 and IE-1 proteins were assessed at multiple time points post SCT, and correlated with the occurrence of CMV reactivation. In a retrospective analysis, recurrent CMV reactivations occurred in 9 patients and were associated with low pp65-specific CD4+ T-cell and low IE-1-specific CD8(+) T-cell reactivities, whereas patients without detectable CMV reactivation (n = 30) or a single reactivation (n = 13) showed a better recovery of these immune responses. CD4+ T-cell responses to IE-1 were infrequent in most patients, whereas CD8+ T-cell responses to pp65 occurred frequently, but did not correlate with protection against (recurrent) reactivation. Prospectively, CMV-specific T-cell responses could be studied prior to 14 reactivation episodes in 8 patients. CD4+ T-cell responses to IE-1 and pp65 were positive in only 1 and 2 episodes, respectively. CD8+ T-cell responses against IE-1 were positive in 4, but against pp65 in 12 episodes, again showing that CD8+ T-cell reactivity against pp65 did not prevent CMV reactivation. Thus, monitoring of particular CMV-specific CD4+ and CD8+ T-cell responses after allogeneic SCT may identify patients at risk for recurrent CMV reactivations.


The prognostic impact of quality of life assessed with the EORTC QLQ-C30 in inoperable non-small cell lung carcinoma treated with radiotherapy.
The purpose of this study was to assess the prognostic significance of pretreatment quality of life (QoL) scores and symptom scores in a group of patients treated with high dose radiotherapy. A total of 198 patients treated with external irradiation (>/=60 Gy) were included. In all these patients, baseline QoL was assessed using the EORTC QLQ-C30. The prognostic significance of a number of non-QoL and QoL parameters with regard to survival was estimated in both univariate and multivariate analyses. In a multivariate model including the non-QoL parameters, performance status, weight loss and N-classification were independent prognostic factors for survival. After entering the QoL parameters in the model, global QoL was the strongest prognostic factor, while performance status lost its significance. Subsequently, a significant interaction term was found between N-classification and global QoL, indicating that global QoL was an independent prognostic factor but that the effect varied as a function of N-status. In N+ patients, the median survival in the group with low scores for global QoL was 4.5 months, which was significantly worse (P<0.0001) compared with the high score group in which the median survival was 12.9 months. Global QoL is a strong prognostic factor for survival in patients with NSCLC who have pathological lymph nodes at presentation and who are treated with radical or curative radiotherapy.


[Persistent symptomatology in workers industrially exposed to organophosphate pesticides].
To describe the patterns of persistent symptomatology in workers industrially exposed to organophosphate pesticides. An observational, descriptive and cross-sectional study was performed. A questionnaire was applied to managers of a factory and to 89 workers, whose erythrocytic cholinesterase level was measured with the Magnotti and Lovibond method. Information is described through rates, central tendency measures and dispersion. Differences between groups were evaluated with the chi 2 test and the odds ratio was calculated. Persistent symptomatology was found in 6.3 per 10 workers. 50% had six or more symptoms. No significant differences were found as to the risk of suffering from persistent symptomatology with respect to age, length of service or position at work. However, the highest proportion of symptoms was found in workers of 31 to 40 years of age, with 6 to 13 years of service, from the maintenance area, working as general operators or supervisors. Among the 13 workers with previous intoxication, the prevalence of persistent symptomatology was 6.9 against 6.1 in workers who had not been intoxicated before. The risk of acute poisoning in workers with more than 14 years of service was 4 times greater than in workers with less than 14 years of service (p < 0.005). Average level of blood cholinesterase was normal (4.4 u/ml). Results show a relationship between exposure to organophosphate pesticides and presence of persistent symptoms. It is necessary to study the prevalence of this symptomatology in exposed and non-exposed populations.


ASSAY OF VITAMINS AND AMINO ACIDS WITH CULTURED TISSUE CELLS AND ANTIMETABOLITES.
A survey of growth responses of tissue-culture cells to vitamins and amino acids was undertaken to explore the potentialities of tissue culture in the assay of growth factors. An antagonist of the nutrient was included in each test system to improve its sensitivity. Addition of an antimetabolite was advantageous in the thiamine and phenylalanine assays. Tissue-culture assays of tryptophan and of phenylalanine supplemented with beta-2-thienylalanine compared favorably with microbial assays, and may serve as confirmatory or supplementary test systems. The sensitivity of cultured tissue cells to minute amounts of a variety of physiologically active substances suggests their employment in hormone and toxic compound assays.


The control of epidermal stem cells (holoclones) in the treatment of massive full-thickness burns with autologous keratinocytes cultured on fibrin.
Cell therapy is an emerging therapeutic strategy aimed at replacing or repairing severely damaged tissues with cultured cells. Epidermal regeneration obtained with autologous cultured keratinocytes (cultured autografts) can be life-saving for patients suffering from massive full-thickness burns. However, the widespread use of cultured autografts has been hampered by poor clinical results that have been consistently reported by different burn units, even when cells were applied on properly prepared wound beds. This might arise from the depletion of epidermal stem cells (holoclones) in culture. Depletion of holoclones can occur because of (i) incorrect culture conditions, (ii) environmental damage of the exposed basal layer of cultured grafts, or (iii) use of new substrates or culture technologies not pretested for holoclone preservation. The aim of this study was to show that, if new keratinocyte culture technologies and/or "delivery systems" are proposed, a careful evaluation of epidermal stem cell preservation is essential for the clinical performance of this life-saving technology. Fibrin was chosen as a potential substrate for keratinocyte cultivation. Stem cells were monitored by clonal analysis using the culture system originally described by Rheinwald and Green as a reference. Massive full-thickness burns were treated with the composite allodermis/cultured autograft technique. We show that: (i) the relative percentage of holoclones, meroclones, and paraclones is maintained when keratinocytes are cultivated on fibrin, proving that fibrin does not induce clonal conversion and consequent loss of epidermal stem cells; (ii) the clonogenic ability, growth rate, and long-term proliferative potential are not affected by the new culture system; (iii) when fibrin-cultured autografts bearing stem cells are applied on massive full-thickness burns, the "take" of keratinocytes is high, reproducible, and permanent; and (iv) fibrin allows a significant reduction of the cost of cultured autografts and eliminates problems related to their handling and transportation. Our data demonstrate that: (i) cultured autografts bearing stem cells can indeed rapidly and permanently cover a large body surface; and (ii) fibrin is a suitable substrate for keratinocyte cultivation and transplantation. These data lend strength to the concept that the success of cell therapy at a clinical level requires cultivation and transplantation of stem cells. We therefore suggest that the proposal of a culture system aimed at the replacement of any severely damaged self-renewing tissue should be preceded by a careful evaluation of its stem cell population.


[Properties of strains of the causative agent of plague resistant to the diagnostic phage L-413 "c"].
The data obtained in the comparative study of the lytic activity of two plague diagnostic phages, Pokrovskaya's phage and phage l-413 "c", with respect to 655 Y. pestis strains are presented. The study revealed the advantage of Pokrovskaya's phage which lyzed all the strains under test over phage l-413 "c", found to be inactive with respect to 27 Y. pestis strains. The properties of the strains resistant to phage l-413 "c" were typical for the causative agent of plague in the corresponding natural foci.


Visual acuity screening of children 6 months to 3 years of age.
The operant preferential looking (OPL) procedure allows a behavioral estimate of visual acuity to be obtained from children 6 mo to 3 yr of age. In clinical settings, there is often too little time available to obtain an acuity estimate with the standard OPL procedure. The goal of this study was to identify specific spatial frequencies, termed diagnostic grating frequencies, that could enable the OPL technique to be used as a screening procedure under conditions where completion of acuity estimation was not possible. One hundred eighty presumptively normal children, 6, 12, 18, 24, 30, and 36 mo of age, were each tested with up to 20 trials of a potential diagnostic grating frequency to determine the highest spatial frequency grating that could be resolved by 90% of children at each age. For all ages except 18 mo, there existed a spatial frequency that produced uniformly high OPL performance within the age group; this spatial frequency was separated by one-half to one octave from a higher spatial frequency that more than 30% of children at that age failed to detect. These results suggest that at all ages except 18 mo, it should be possible to use the OPL procedure as a vision screening tool by testing individual children with the diagnostic grating frequency appropriate for their age.


Cost of Myopia Correction: A Systematic Review.
Myopia is one of the leading causes of visual impairment globally. Despite increasing prevalence and incidence, the associated cost of treatment remains unclear. Health care spending is a major concern in many countries and understanding the cost of myopia correction is the first step eluding to the overall cost of myopia treatment. As cost of treatment will reduce the burden of cost of illness, this will aid in future cost-benefit analysis and the allocation of healthcare resources, including considerations in integrating eye care (refractive correction with spectacles) into universal health coverage (UHC). We performed a systematic review to determine the economic costs of myopia correction. However, there were few studies for direct comparison. Costs related to myopia correction were mainly direct with few indirect costs. Annual prevalence-based direct costs for myopia ranged from $14-26 (USA), $56 (Iran) and $199 (Singapore) per capita, respectively (population: 274.63 million, 75.15 million and 3.79 million, respectively). Annually, the direct costs of contact lens were $198.30-$378.10 while spectacles and refractive surgeries were $342.50 and $19.10, respectively. This review provides an insight to the cost of myopia correction. Myopia costs are high from nation-wide perspectives because of the high prevalence of myopia, with contact lenses being the more expensive option. Without further interventions, the burden of illness of myopia will increase substantially with the projected increase in prevalence worldwide. Future studies will be necessary to generate more homogenous cost data and provide a complete picture of the global economic cost of myopia.


An anthropometric model to estimate neonatal fat mass using air displacement plethysmography.
Current validated neonatal body composition methods are limited/impractical for use outside of a clinical setting because they are labor intensive, time consuming, and require expensive equipment. The purpose of this study was to develop an anthropometric model to estimate neonatal fat mass (kg) using an air displacement plethysmography (PEA POD® Infant Body Composition System) as the criterion. A total of 128 healthy term infants, 60 females and 68 males, from a multiethnic cohort were included in the analyses. Gender, race/ethnicity, gestational age, age (in days), anthropometric measurements of weight, length, abdominal circumference, skin-fold thicknesses (triceps, biceps, sub scapular, and thigh), and body composition by PEA POD® were collected within 1-3 days of birth. Backward stepwise linear regression was used to determine the model that best predicted neonatal fat mass. The statistical model that best predicted neonatal fat mass (kg) was: -0.012 -0.064*gender + 0.024*day of measurement post-delivery -0.150*weight (kg) + 0.055*weight (kg)2 + 0.046*ethnicity + 0.020*sum of three skin-fold thicknesses (triceps, sub scapular, and thigh); R2 = 0.81, MSE = 0.08 kg. Our anthropometric model explained 81% of the variance in neonatal fat mass. Future studies with a greater variety of neonatal anthropometric measurements may provide equations that explain more of the variance.


Ameliorative effect of ozone on cytokine production in mice injected with human rheumatoid arthritis synovial fibroblast cells.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by invasion of hyperplastic synovial cells and progressive joint destruction. Ozone therapy has been proposed as an immunomodulator and cellular metabolic activator which shows long-term anti-inflammatory effects and serves to reduce further the proinflammatory factors. We purified RA synovial fibroblast cells (RA-SFc) from patients and avoided contaminating macrophages by flow cytometry, then treated them with ozone. Following the observable decreased production of proinflammatory factors TNF-alpha, IL-1beta, and IL-6 from RA-SFc, we infused the cultured RA-SFc into joints of severe combined immunodeficiency mice. The mRNA and protein levels of the RA-SFc exposed to 3% and 5% ozone were the same. As a result, 3% and 5% ozone applied externally ameliorated the inflammatory reaction of RA without toxicity or serious side effects. Therefore, ozone injected into the knees of RA patients could become a valuable treatment, and we confirm the interactive mechanism between ozone and RA-SFc.


Drug therapy to aid in smoking cessation. Tips on maximizing patients' chances for success.
The arsenal of pharmacologic agents available for smoking cessation has expanded in the last few years, and it is likely to continue to do so. It is important that practicing physicians keep abreast of new methods as they become available and encourage patients who smoke to undertake cessation measures. Nicotine-replacement therapy is available in gum, patch, nasal spray, or inhaler form, and bupropion therapy aids in smoking cessation through dopaminergic activity. The foundation of effective intervention is likely to remain unchanged: an individualized plan addressing behavioral, addictive, pharmacologic, and relapse-prevention components. In addition to the necessary information about treatment choices, physicians should offer motivation, support, and follow-up to their patients who wish to quit smoking.


Efficacy of a multilevel intervention on the mental health of people living with HIV and their family members in rural China.
HIV has a profound impact on infected individuals and their families. This study evaluated the efficacy of an intervention aimed at improving the mental health of people living with HIV (PLH) and their family members. A randomized controlled trial of 475 PLH and 522 family members was conducted in Anhui, China. The intervention comprised activities at individual, family, and community levels. The study outcomes, which included depressive symptoms and coping with illness for the PLH and depressive symptoms and caregiver burden for the family members, were assessed at baseline and at 6-, 12-, 18-, and 24-month follow-up. We used a mixed-effects regression model with village- and participant-level random effects to assess the intervention effect on the improvement of outcome measures. Relative to the control condition, the PLH and family members of the intervention group reported a significant reduction in depressive symptoms. The largest difference in depressive symptoms was observed at 6 months for the PLH and at 12 months for family members. Decreases in perceived caregiver burden over time were observed for family members in both conditions; however, the group difference did not reach statistical significance. Significant intervention effect on the coping with illness was reported by the PLH. The study highlights the importance of empowering families affected by HIV to confront the challenges together rather than individually. It may be optimal for future programs to include both PLH and their family members to maximize intervention effects through strengthening interactions and support within a family. (PsycINFO Database Record


Estimation of gross α-β and tritium activities in groundwater samples using LSC-TDCR technique in and around the geothermal region of Eastern India.
The present study is an attempt to assess the radiogenic quality of groundwater on the basis of gross α, gross β and tritium (3H or H-3) activities in the Bakreswar-Tantloi geothermal region of Chotanagpur Plateau, West Bengal and Jharkhand, India. The aforesaid parameters in groundwater samples were measured using liquid scintillation counting triple to double coincidence ratio (LSC-TDCR) technique. Groundwater samples collected from Bakreswar-Tantloi geothermal region show gross α activities from below the minimum detectable activity (BMDA) to 0.5 ± 0.05 Bq/L, gross β activities from BMDA to 0.2 ± 0.01 Bq/L and H-3 activities from BMDA to 63.42 Bq/L. The average gross α, gross β and H-3 activities are also within the permissible limits prescribed by the World Health Organization (WHO). Though the annual effective doses in some samples were higher than the reference dose level of 0.1 mSv, the overall result suggests that the groundwater in the Bakreswar-Tantloi geothermal region is radiologically safe considering the radionuclides covered in this study.


Haplotype-resolved genome of heterozygous African cassava cultivar TMEB117 (Manihot esculenta).
Cassava (Manihot esculenta Crantz) is a vital tropical root crop providing essential dietary energy to over 800 million people in tropical and subtropical regions. As a climate-resilient crop, its significance grows as the human population expands. However, yield improvement faces challenges from biotic and abiotic stress and limited breeding. Advanced sequencing and assembly techniques enabled the generation of a highly accurate, nearly complete, haplotype-resolved genome of the African cassava cultivar TMEB117. It is the most accurate cassava genome sequence to date with a base-level accuracy of QV > 64, N50 > 35 Mbp, and 98.9% BUSCO completeness. Over 60% of the genome comprises repetitive elements. We predicted over 45,000 gene models for both haplotypes. This achievement offers valuable insights into the heterozygosity genome organization of the cassava genome, with improved accuracy, completeness, and phased genomes. Due to its high susceptibility to African Cassava Mosaic Virus (ACMV) infections compared to other cassava varieties, TMEB117 provides an ideal reference for studying virus resistance mechanisms, including epigenetic variations and smallRNA expressions.


Crystal structure of flavodoxin from Desulfovibrio desulfuricans ATCC 27774 in two oxidation states.
The crystal structures of the flavodoxin from Desulfovibrio desulfuricans ATCC 27774 have been determined and refined for both oxidized and semi-reduced forms to final crystallographic R-factors of 17.9% (0.8-0.205-nm resolution) and 19.4% (0.8-0.215-nm resolution) respectively. Native flavodoxin crystals were grown from ammonium sulfate with cell constants a = b = 9.59 nm, c=3.37nm (oxidized crystals) and they belong to space group P3(2)21. Semireduced crystals showed some changes in cell dimensions: a = b = 9.51 nm, c=3.35 nm. The three-dimensional structures are similar to other known flavodoxins and deviations are found essentially in the isoalloxazine ring environment. Conformational changes are observed between both redox states and a flip of the Gly61-Met62 peptide bond occurs upon one-electron reduction of the FMN group. These changes influence the redox potential of the oxidized/semiquinone couple. Modulation of the redox potentials is known to be related to the association constant of the FMN group to the protein. The flavodoxin from D. desulfuricans now studied has a large span between E2 (oxidized --> semiquinone) and E1 (semiquinone --> hydroquinone) redox potentials, both these values being substantially more positive within known flavodoxins. A comparison of their FMN environment was made in both oxidation states in order to correlate functional and structural differences.


Modulation of EGF receptor protooncogene expression by growth factors and hormones in human breast carcinoma cells.
In this review I summarize the experimental data in favor of the notion that control of epidermal growth factor (EGF) receptor (R) and/or c-erbB-2 protooncogene expression by specific autocrine growth factors and certain classical endocrine hormones serves as a transducer of extracellular signals that ultimately lead to growth responses in breast carcinoma cells. I summarize some new results on the role of epidermal growth factor (EGF), transforming growth factor (TGF) alpha, and TGF beta in the control of EGF-R protooncogene expression in human breast carcinoma cells. Furthermore, the data embracing the hypothesis that the growth actions of hormone receptors that are homologous to the v-erbA oncogene (estrogens, progesterone, thyroid hormones, retinoic acid, and vitamin D) are mediated, in part, by modulating EGF-R and/or c-erbB-2 protooncogene transcription are reviewed. Finally, I develop the theme that cooperation of certain c-erb-A-related, c-erbB-2 and/or EGF-R gene products contribute to the uncontrolled growth of human mammary carcinoma cells. From the evidence reviewed, one can infer that elucidation of the molecular control of EGF-R/c-erbB-2 gene expression by c-erbA-related gene products may lead to both a better understanding of breast carcinogenesis and a new therapeutic approach directed at controlling the transcriptional responses of EGF-R/c-erbB-2 genes.


Parasite-infected sticklebacks increase the risk-taking behaviour of uninfected group members.
Trophically transmitted parasites frequently increase their hosts' risk-taking behaviour, to facilitate transmission to the next host. Whether such elevated risk-taking can spill over to uninfected group members is, however, unknown. To investigate this, we confronted groups of 6 three-spined sticklebacks, Gasterosteus aculeatus, containing 0, 2, 4 or 6 experimentally infected individuals with a simulated bird attack and studied their risk-taking behaviour. As a parasite, we used the tapeworm Schistocephalus solidus, which increases the risk-taking of infected sticklebacks, to facilitate transmission to its final host, most often piscivorous birds. Before the attack, infected and uninfected individuals did not differ in their risk-taking. However, after the attack, individuals in groups with only infected members showed lower escape responses and higher risk-taking than individuals from groups with only uninfected members. Importantly, uninfected individuals adjusted their risk-taking behaviour to the number of infected group members, taking more risk with an increasing number of infected group members. Infected individuals, however, did not adjust their risk-taking to the number of uninfected group members. Our results show that behavioural manipulation by parasites does not only affect the infected host, but also uninfected group members, shedding new light on the social dynamics involved in host-parasite interactions.


[Hypersensitivity reactions to use of mebeverine].
Twenty-one cases of adverse reactions to mebeverine use were reported to the Inspectorate for Health Care in the Netherlands since 1978. In 12 patients (five men and seven women) this was an immunological hypersensitivity reaction. All patients recovered after drug withdrawal. The time between start and onset of symptoms varied from several minutes to 14 days. Most reactions consisted of urticaria or maculopapular rash, sometimes accompanied by fever, polyarthritis, thrombopenia or angioedema. In contradiction to the manufacturer's claims adverse reactions to the use of mebeverine do occur.


Polyclonal adaptive regulatory CD4 cells that can reverse type I diabetes become oligoclonal long-term protective memory cells.
Type 1 diabetes is a CD4 cell-dependent disease that results from destruction of insulin-producing beta cells in pancreatic islets. An ideal therapy would reverse diabetes shortly after onset when islet function in not yet fully ablated, and also prevent re-emergence of disease through the generation of memory cells that control the autoimmune response. In this study, we show that adaptive/induced polyclonal regulatory (TR) cells, which contain islet-reactive cells, fulfill these criteria in the NOD mouse model. CD4 cells induced to express FoxP3, IL-10, and TGF-beta1 in response to TCR signaling and TGF-beta1 can reverse diabetes with clinical restoration of prediabetic serum levels of IL-10. Unlike naturally occurring TR cells, these adaptive TR cells persist indefinitely (>1 year) as FoxP3(+), CD25(-) memory cells that self-renew. Establishment of memory is accompanied by narrowing of the T cell repertoire to usage of a single TCR beta-chain, Vbeta11, implying selection by Ag. With islet-specific adaptive TR cells, we show that memory is functionally stable and transferable. Therefore, adaptive TR cells, which can be readily generated from normal CD4 populations and become focused by Ag with induction of memory, may provide a treatment and a vaccine for the long-term cure of diabetes making them attractive as immunotherapeutic agents.


Phylogenetic conservation of glycoprotein 96 ability to interact with CD91 and facilitate antigen cross-presentation.
Although the ability of gp96 to activate APCs and generate CD8 CTLs against peptides they chaperone through interaction with the endocytic receptors CD91 is supported by solid evidence, its biological relevance in immune surveillance is debated. We have used an evolutionary approach to determine whether gp96 interacts with receptors expressed on APCs and promotes MHC class I cross-presentation of minor histocompatibility Ags (H-Ags) to CTLs in the frog Xenopus. We show that in Xenopus gp96 binds the CD91 homolog at the surface of peritoneal leukocytes, and that this binding is inhibited by molar excess of unlabeled gp96 or the CD91 ligand alpha2-macroglobulin, by anti-CD91 Ab and by the specific CD91 antagonist receptor-associated protein. Surface binding followed by internalization of gp96 was confirmed by fluorescent microscopy. Furthermore, adoptive transfer of peritoneal leukocytes pulsed with as little as 800 ng of gp96 chaperoning minor H-Ags, but not minor H-Ag-free gp96, induces potent CD8 T cell infiltration and Ag-specific accelerated rejection of minor H-locus disparate skin grafts. Inhibition of gp96-CD91 interaction by pretreatment with anti-CD91 Ab and receptor-associated protein impairs both CD8 T cell infiltration and acute skin graft rejection. These data provide evidence of the conserved ability of gp96 to facilitate cross-presentation of chaperoned Ags by interacting with CD91. The persistence of this biological process for >350 million years that separate mammals and amphibians from a common ancestor strongly supports the proposition that gp96 and CD91 are critically involved in immune surveillance.


Impact of a Prenatal Vitamin D Supplementation Program on Vitamin D Deficiency, Rickets and Early Childhood Caries in an Alaska Native Population.
Background: Early childhood rickets increased in Alaska Native children after decreases in vitamin D-rich subsistence diet in childbearing-aged women. We evaluated the impact of routine prenatal vitamin D supplementation initiated in Alaska's Yukon Kuskokwim Delta in Fall 2016. Methods: We queried electronic health records of prenatal women with 25(OH) vitamin D testing during the period 2015−2019. We evaluated 25(OH)D concentrations, vitamin D3 supplement refills, and decayed, missing, and filled teeth (dmft) scores and rickets in offspring. Results: Mean 25(OH)D concentrations increased 36.5% from pre- to post-supplementation; the percentage with deficient 25(OH)D decreased by 66.4%. Women with ≥ 60 vitamin D3 refill days had higher late pregnancy 25(OH)D concentrations than those with no refill days (p < 0.0001). Women with late pregnancy insufficient 25(OH)D concentrations had offspring with higher dmft scores than those with sufficient 25(OH)D (RR 1.3, p < 0.0001). Three children were diagnosed with nutritional rickets during the period 2001−2021, and none after 2017. Conclusions: These findings suggest that prenatal vitamin D supplementation can improve childhood outcomes in high-risk populations with high rates of rickets.


Severe tuberculosis requiring ICU admission.
Tuberculosis is a curable disease that can evolve to severe forms, requiring the treatment of the patients in an ICU, especially if there is a delay in the diagnosis or if it affects elderly patients, those on dialysis, or those with HIV infection or other states of immunosuppression, as well as in cases of multidrug resistant disease. Knowledge of the radiological presentation of the cases can help diagnose these severe forms, as can the introduction of new tests, such as the early detection of the etiological agent by PCR and chest CT, which favors the early initiation of treatment. In addition, the use of regimens without isoniazid and rifampin, as well as uncertain enteral absorption and low serum concentrations of antituberculosis drugs, can reduce the efficacy of treatment. For such patients, the prognosis is generally poor and mortality rates are high.


Biogenesis of Salmonella typhimurium-containing vacuoles in epithelial cells involves interactions with the early endocytic pathway.
In epithelial cells, the intracellular pathogen Salmonella typhimurium resides and replicates within a unique cytoplasmic organelle, the Salmonella-containing vacuole (SCV). In vitro studies have shown that the SCV is a dynamic organelle that selectively acquires lysosomal glycoproteins (Igps) without fusing directly with lyosomes. Here, we have investigated early events in SCV biogenesis using immunofluorescence microscopy and epitope-specific flow cytometry. We show that proteins specific to the early endocytic pathway, EEA1 and transferrin receptor (TR), are present on early SCVs. The association of these proteins with SCVs is transient, and both proteins are undetectable at later time points when Igp and vATPase are acquired. Analysis of the fraction of SCVs containing both TR and lamp-1 showed that TR is lost from SCVs as the Igp is acquired, and that these processes occur progressively and not as the result of a single fusion/fission event. These experiments reveal a novel mechanism of SCV biogenesis, involving previously undetected initial interactions with the early endocytic pathway followed by the sequential delivery of Igp. The pathway does not involve interactions with the late endosome/prelysosome and is distinct from traditional phagocytic and endocytic pathways. Our study indicates that intracellular S. typhimurium occupies a unique niche, branching away from the traditional endocytic pathway between the early and late endosomal compartments.


Which specimens from a museum collection will yield DNA barcodes? A time series study of spiders in alcohol.
We report initial results from an ongoing effort to build a library of DNA barcode sequences for Dutch spiders and investigate the utility of museum collections as a source of specimens for barcoding spiders. Source material for the library comes from a combination of specimens freshly collected in the field specifically for this project and museum specimens collected in the past. For the museum specimens, we focus on 31 species that have been frequently collected over the past several decades. A series of progressively older specimens representing these 31 species were selected for DNA barcoding. Based on the pattern of sequencing successes and failures, we find that smaller-bodied species expire before larger-bodied species as tissue sources for single-PCR standard DNA barcoding. Body size and age of oldest successful DNA barcode are significantly correlated after factoring out phylogenetic effects using independent contrasts analysis. We found some evidence that extracted DNA concentration is correlated with body size and inversely correlated with time since collection, but these relationships are neither strong nor consistent. DNA was extracted from all specimens using standard destructive techniques involving the removal and grinding of tissue. A subset of specimens was selected to evaluate nondestructive extraction. Nondestructive extractions significantly extended the DNA barcoding shelf life of museum specimens, especially small-bodied species, and yielded higher DNA concentrations compared to destructive extractions. All primary data are publically available through a Dryad archive and the Barcode of Life database.


Characterization and comparison of the DNAs of the three closely related bacteriophages gd, ge and gf with the genome DNA of the hydrogen-oxidizing host strain Pseudomonas pseudoflava GA3.
The double-stranded (ds)DNAs of the three closely related temperate Pseudomonas pseudoflava bacteriophages gd, ge and gf were studied biochemically and biophysically. The GC content of the DNA was 67.4 +/- 0.5% and differed only slightly from that of the host P. pseudoflava. By electron microscopic length measurements a mol. wt. of 26.1 X 10(6) to 26.7 X 10(6) was calculated for the three bacteriophage DNAs. Homogeneity of the bacteriophage DNAs was further demonstrated by specific cleavage with restriction endonucleases WcoRI and HindIII. It was concluded that the three homo-immune bacteriophages are identical. The genome size of the host P. pseudoflava GA3 was 3.7 X 10(9) as calculated from optical renaturation rate measurement with Xanthomonas pelargonii reference DNA. The bacteriophage gd genome thus amounts to 0.7% of the chromosome of this bacterial host.


Dietary Antioxidants and Longitudinal Changes in Lower Urinary Tract Symptoms in Elderly Men: The Osteoporotic Fractures in Men Study.
Antioxidants can potentially alter the progression of lower urinary tract symptoms (LUTS) through anti-inflammatory mechanisms. To determine if dietary antioxidants are associated with reduced likelihood of LUTS progression or increased likelihood of LUTS remission in untreated elderly men. A prospective cohort study of 1670 US men aged 65-100 yr. Baseline variables included the American Urological Association Symptom Index, dietary intake assessed via a 69-item Block food frequency questionnaire (FFQ), demographics, lifestyle characteristics, quality of life (SF-12), and medication use. LUTS was assessed at four time points over a mean ± standard deviation period of 6.9±0.4 yr. Group-based trajectory modeling was performed for men without prostate cancer who did not undergo LUTS treatment with medication or surgery during follow-up (n=1670). Analyses were stratified by LUTS symptoms at baseline. For men with mild baseline LUTS, we examined the likelihood of LUTS progression relative to LUTS stability. For men with moderate baseline LUTS, we analyzed the likelihood of both LUTS progression relative to LUTS stability and LUTS remission relative to progression. Odds ratios and 95% confidence intervals were estimated for quartiles of daily antioxidant intake using multivariable logistic regression. None of the dietary antioxidants (vitamin C, vitamin E, β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein/zeaxanthin) was associated with a lower probability of LUTS progression or LUTS remission. The study was limited by use of the brief Block FFQ, which contains only 69 food items and may have biased results toward the null hypothesis because of nondifferential misclassification. In this large cohort of US men, there were no significant associations between multiple dietary antioxidants and LUTS progression or remission over 7 yr. In a large cohort of elderly men, there were no significant longitudinal associations between multiple dietary antioxidants and lower urinary tract symptoms (LUTS). Our data suggest that dietary antioxidant consumption may not influence the natural history of LUTS in older men.


Metabolism of xenobiotic compounds by enzymes in cell extracts of the fungus Cunninghamella elegans.
Cell extracts of the filamentous fungus Cunninghamella elegans contain epoxide hydrolase (EC 22.214.171.124), glutathione S-transferase (EC 184.108.40.206) and UDP-glucuronosyltransferase (EC 18.104.22.168) activities. Epoxide hydrolase activity was determined with p-nitrostyrene oxide as substrate and was shown to be associated with the 100 000 g pellet obtained from disrupted mycelia. Glutathione S-transferase activity was demonstrated with 1-chloro-2,4-dinitrobenzene and p-nitrobenzyl chloride as substrates. The presence of two or more glutathione S-transferase activities was indicated by different activity ratios for the two substrates in different extracts, and by distinct thermal denaturation curves. UDP-glucuronosyltransferase activity with 3-hydroxybenzo[a]pyrene as substrate was found only with the non-sedimentable fraction prepared from ruptured mycelia.


Mechanism of Holliday junction resolution by the human GEN1 protein.
Holliday junction (HJ) resolution is essential for chromosome segregation at meiosis and the repair of stalled/collapsed replication forks in mitotic cells. All organisms possess nucleases that promote HJ resolution by the introduction of symmetrically related nicks in two strands at, or close to, the junction point. GEN1, a member of the Rad2/XPG nuclease family, was isolated recently from human cells and shown to promote HJ resolution in vitro and in vivo. Here, we provide the first biochemical/structural characterization of GEN1, showing that, like the Escherichia coli HJ resolvase RuvC, it binds specifically to HJs and resolves them by a dual incision mechanism in which nicks are introduced in the pair of continuous (noncrossing) strands within the lifetime of the GEN1-HJ complex. In contrast to RuvC, but like other Rad2/XPG family members such as FEN1, GEN1 is a monomeric 5'-flap endonuclease. However, the unique feature of GEN1 that distinguishes it from other Rad2/XPG nucleases is its ability to dimerize on HJs. This functional adaptation provides the two symmetrically aligned active sites required for HJ resolution.


Acute and short-term effects of new calcium antagonist in hypertension.
Nitrendipine (Bay e 5009) is a new calcium antagonist antihypertensive agent similar in structure and function to nifedipine. Nitrendipine was tested in a range of single and repeated doses in 10 adult males with uncomplicated mild to moderate hypertension. The treatment goal was reduction of diastolic blood pressure to 90 mm Hg or less. The dose that achieved goal blood pressure ranged between 10 and 30 mg. Systolic and diastolic blood pressure began to fall within 15 minutes following ingestion of single oral doses of nitrendipine. The maximum effect of the drug was achieved in 60 to 90 minutes and remained at approximately this level for 6 to 8 hours. The average reduction in supine diastolic was more than twice as great as the fall in systolic blood prere began to fall within 15 minutes following ingestion of single oral doses of nitrendipine. The maximum effect of the drug was acheived in 60 to 90 minutes and remained at approximately this level for 6 to 8 hours. The average reduction in supine diastolic was more than twice as great as the fall in systolic blood pressure. With continuous doses given three times daily, all patients' blood pressures were as low or lower than the maximal effect observed after single doses. The reduction in blood pressure was sustained for the full 3 weeks of treatment. There was a sustained small increase in pulse rate averaging 6 beats/min. The drug was generally well tolerated by most patients. Mild to moderate headache that resolved with continued treatment was the most frequent side effect. This preliminary trial indicates that nitrendipine is an effective antihypertensive agent that merits further study.


The Children's Health Exposure Analysis Resource: enabling research into the environmental influences on children's health outcomes.
The Children's Health Exposure Analysis Resource (CHEAR) is a new infrastructure supported by the National Institute of Environmental Health Sciences to expand the ability of children's health researchers to include analysis of environmental exposures in their research and to incorporate the emerging concept of the exposome. There is extensive discussion of the potential of the exposome to advance understanding of the totality of environmental influences on human health. Children's health is a logical choice to demonstrate the exposome concept due to the extensive existing knowledge of individual environmental exposures affecting normal health and development and the short latency between exposures and observable phenotypes. Achieving this demonstration will require access to extensive analytical capabilities to measure a suite of exposures through traditional biomonitoring approaches and to cross-validate these with emerging exposomic approaches. CHEAR is a full-service exposure assessment resource, linking up-front consultation with both laboratory and data analysis. Analyses of biological samples are intended to enhance studies by including targeted analysis of specific exposures and untargeted analysis of small molecules associated with phenotypic endpoints. Services provided by CHEAR are made available without cost but require a brief application and adherence to policies detailed on the CHEAR web page at https://chearprogram.org/.


Routine Histopathological Examination of the Specimen After Laparoscopic Cholecystectomy: Can We Be Brave Enough to Give Up?
Selective versus routine histopathological examination after cholecystectomy is still in debate. This study aims to investigate the effect of histopathology results on treatment modality and surgery strategy. The validity of the selective histopathology approach was questioned. The data of patients undergoing laparoscopic cholecystectomy between January 2009 and December 2019 were retrospectively analyzed. The demographics and histopathology results, whether the operation was emergent or elective, and the reasons for conversion to open surgery were recorded. Malignant and precursor histopathology diagnoses were examined, and their relationship with the surgical strategy was questioned. A total of 2723 patients were included in the study. Of these patients, 2600 (95.5%) were operated under elective, while 123 (4.5%) were operated under emergency conditions. While the surgery was completed laparoscopically in 2685 (98.6%) patients, it was converted to open surgery in 38 (1.4%) patients. Age, gender, the presence of primary gallbladder cancer, acute cholecystitis, and xanthogranulomatous cholecystitis in histopathological examination were found to be independent predictive factors for conversion to open surgery (P < .05). The rate of primary invasive carcinoma in the series was 0.1%. Routine histopathological examination of the gallbladder is important for demonstrating a wide spectrum of pathological changes in this organ. Invasive cancer or precursor lesions can be detected even in patients without any macroscopic abnormality. Histopathological examination also plays a role in determining follow-up, further examination, and treatment modality in addition to the diagnosis in these patients.


Investigating the cost-effectiveness of videotelephone based support for newly diagnosed paediatric oncology patients and their families: design of a randomised controlled trial.
Providing ongoing family centred support is an integral part of childhood cancer care. For families living in regional and remote areas, opportunities to receive specialist support are limited by the availability of health care professionals and accessibility, which is often reduced due to distance, time, cost and transport. The primary aim of this work is to investigate the cost-effectiveness of videotelephony to support regional and remote families returning home for the first time with a child newly diagnosed with cancer We will recruit 162 paediatric oncology patients and their families to a single centre randomised controlled trial. Patients from regional and remote areas, classified by Accessibility/Remoteness Index of Australia (ARIA+) greater than 0.2, will be randomised to a videotelephone support intervention or a usual support control group. Metropolitan families (ARIA+ < or = 0.2) will be recruited as an additional usual support control group. Families allocated to the videotelephone support intervention will have access to usual support plus education, communication, counselling and monitoring with specialist multidisciplinary team members via a videotelephone service for a 12-week period following first discharge home. Families in the usual support control group will receive standard care i.e., specialist multidisciplinary team members provide support either face-to-face during inpatient stays, outpatient clinic visits or home visits, or via telephone for families who live far away from the hospital. The primary outcome measure is parental health related quality of life as measured using the Medical Outcome Survey (MOS) Short Form SF-12 measured at baseline, 4 weeks, 8 weeks and 12 weeks. The secondary outcome measures are: parental informational and emotional support; parental perceived stress, parent reported patient quality of life and parent reported sibling quality of life, parental satisfaction with care, cost of providing improved support, health care utilisation and financial burden for families. This investigation will establish the feasibility, acceptability and cost-effectiveness of using videotelephony to improve the clinical and psychosocial support provided to regional and remote paediatric oncology patients and their families.


Antioxidant potential and transferrin, ceruloplasmin, and lipid peroxidation levels in women with preeclampsia.
The aim of this study was to evaluate lipid peroxidation and antioxidant function in patients with preeclampsia and in normotensive pregnant women and to assess an association with the severity of the disease. Twenty-one patients with mild preeclampsia, 15 patients with severe preeclampsia, and 19 normotensive pregnant women were included in the study. Plasma antioxidant potential (AOP) status, ceruloplasmin (Cp) and transferrin (Trf) levels as antioxidants, and malondialdehyde (MDA) levels as an indicator of lipid peroxidation were measured. Whereas the AOP and Trf levels of the severe and mild preeclampsia groups were found to be reduced, the MDA and Cp levels were increased compared with those of the normotensive pregnant group. There were statistically significant negative correlations between AOP and MDA in all groups. No differences were observed between the groups with severe and mild preeclampsia with respect to these analytes. Our findings suggest that lipid peroxidation may be an important factor in the pathogenesis of preeclampsia and that plasma antioxidants and oxidants are altered in preeclampsia. However, these findings may not be useful in distinguishing women with severe and mild preeclampsia.


Voluntary running influences the efficacy of fluoxetine in a model of postpartum depression.
Postpartum depression affects approximately 15% of mothers. Unfortunately, treatment options for postpartum depression are limited. Pharmacological antidepressants such as fluoxetine (FLX) can be controversial due to inconclusive evidence of efficacy during the postpartum and concerns of neonatal exposure to antidepressants. Alternatively, non-pharmacological antidepressants such as exercise may be less controversial but its efficacy in postpartum depression is unclear. To investigate this, we treated rat dams daily with high levels of corticosterone (CORT; 40 mg/kg), to induce a depressive-like phenotype, or oil (vehicle for CORT) during the postpartum period. Within the oil and CORT conditions, four additional antidepressant conditions were created: 1. FLX (10 mg/kg) + exercise (voluntary access to running wheel); 2. FLX + no exercise; 3. Saline (vehicle for FLX) + exercise; 4. Saline + No exercise. We examined maternal care, depressive-like and anxiety-like behavior, stress reactivity, and hippocampal neurogenesis and dams were categorized as "high running" or "low running." FLX treatment, alone or with high running, prevented CORT-induced disruptions in maternal care. As expected, CORT increased depressive-like behavior but exercise, regardless of running amount, reduced depressive-like behavior. Intriguingly, FLX, but not CORT, increased anxiety-like behavior, which was not mitigated by concurrent exercise. FLX treatment slightly but significantly facilitated serum CORT recovery after forced swim stress. CORT and FLX alone reduced neurogenesis, while exercise coupled with FLX increased density of doublecortin-expressing cells. High running increased density of doublecortin-expressing cells (immature neurons) in comparison to controls. Collectively, these findings indicate that FLX and exercise reverse different endophenotypes of depression in dams, which has translational implications for surveying treatment options of postpartum depression.


The spatial, temporal and contrast properties of expansion and rotation flight optomotor responses in Drosophila.
Fruit flies respond to panoramic retinal patterns of visual expansion with robust steering maneuvers directed away from the focus of expansion to avoid collisions and maintain an upwind flight posture. Panoramic rotation elicits comparatively weak syndirectional steering maneuvers, which also maintain visual stability. Full-field optic flow patterns like expansion and rotation are elicited by distinct flight maneuvers such as body translation during straight flight or body rotation during hovering, respectively. Recent analyses suggest that under some experimental conditions the rotation optomotor response reflects the linear sum of different expansion response components. Are expansion and rotation-mediated visual stabilization responses part of a single optomotor response subserved by a neural circuit that is differentially stimulated by the two flow fields, or rather do the two behavioral responses reflect two distinct control systems? Guided by the principle that the properties of neural circuits are revealed in the behaviors they mediate, we systematically varied the spatial, temporal and contrast properties of expansion and rotation stimuli, and quantified the time course and amplitude of optomotor responses during tethered flight. Our results support the conclusion that expansion and rotation optomotor responses are indeed two separate reflexes, which draw from the same system of elementary motion detectors, but are likely mediated by separate pre-motor circuits having different spatial integration properties, low-pass characteristics and contrast sensitivity.


Immunohistochemical comparison of chordoma with chondrosarcoma, myxopapillary ependymoma, and chordoid meningioma.
Chordoma originates from embryonic notochordal remnants in the midline along the spinal axis and is characterized by cords and lobules of neoplastic cells arranged within myxoid matrix. Because of histologic similarities with myxoid matrix and overlapping immunohistochemical profile, chondrosarcoma, myxopapillary ependymoma, and chordoid meningioma enter in the histologic differential diagnosis at this site. Therefore, the judicious use of a panel of selected immunostains is unquestionably helpful in diagnostically challenging cases. To find useful immunohistochemical markers for assisting in differential diagnosis between chordoma and other tumors with chordoid morphology, an immunohistochemical study using D2-40, epithelial membrane antigen (EMA), pan-cytokeratin (panCK), glial fibrillary acidic protein (GFAP), S-100 protein, galectin-3, neural cell adhesion molecule (NCAM), beta-catenin, E-cadherin, and carcinoembryonic antigen was performed on 14 chordomas, 7 chondrosarcomas, 9 myxopapillary ependymomas, and 4 chordoid meningiomas. Chordoma typically showed positive for EMA and panCK and negative for D2-40 and GFAP; whereas chondrosarcoma revealed positive for D2-40, and negative for EMA, panCK, and GFAP; myxopapillary ependymoma positive for GFAP and negative for EMA; and chordoid meningioma positive for EMA, and negative for panCK and GFAP. On the basis of our immunohistochemical study, a panel of D2-40, EMA, panCK, and GFAP allowed the correct recognition of all tumors examined. Other immunohistochemical markers including S-100 protein, galectin-3, NCAM, beta-catenin, E-cadherin, and carcinoembryonic antigen were of little value in differential diagnosis. In summary, the best immunohistochemical markers useful for the evaluation of tumors with chordoid morphology were D2-40, EMA, cytokeratin, and GFAP. D2-40 was a true chondroid marker to be useful for the differential diagnosis with chordoma.


An analysis of predictive factors for the conversion from premature thelarche into complete central precocious puberty.
To determine the predictive factors for the conversion of premature thelarche (PT) into complete central precocious puberty (CCPP) in girls. Prospective. One hundred and fifty-one girls with PT referred consecutively for evaluation of clinical, laboratory, and ultrasound data. Twenty-one and a half percent of girls with PT converted into CCPP at a chronological age of 7.1 +/- 0.7 years and bone age of 9.0 +/- 1.1 years. Using logistic regression analysis, longitudinal diameter of uterus (OR = 1.215), Tanner breast stage at the time of first physical examination (OR = 3.334) and regression of breast development (OR = 3.921) were the most significant variables predicting the conversion from PT into CCPP. Compared with the non-converted group, the converted groups had larger breast size at the time of diagnosis (z = 2.077, p = 0.038). A total of 69.5% (105/151) of patients experienced complete regression of breast development, 13.2% (14/105) of whom converted into CCPP; 21.5% (31/151) of patients had recurrent breast development, 32.3% (10/31) of whom converted into CCPP; 10% (15/151) of patients had constant breast development, 56.7% (7/15) of whom converted into CCPP, with the highest rate among the three breast development categories (chi2 = 12.23, p = 0.002). PT is not often a self-limited condition and may sometimes convert into CCPP. The predictive factors for conversion were related to estrogen exposure including longitudinal diameter of the uterus, Tanner breast stage at the first consultation and the regressive categories of breast development.


Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia.
Autosomal recessive cerebellar ataxias are a group of neurodegenerative disorders that are characterized by complex clinical and genetic heterogeneity. Although more than 20 disease-causing genes have been identified, many patients are still currently without a molecular diagnosis. In a two-generation autosomal recessive cerebellar ataxia family, we mapped a linkage to a minimal candidate region on chromosome 16p13.3 flanked by single-nucleotide polymorphism markers rs11248850 and rs1218762. By combining the defined linkage region with the whole-exome sequencing results, we identified a homozygous mutation (c.493CT) in CHIP (NM_005861) in this family. Using Sanger sequencing, we also identified two compound heterozygous mutations (c.389AT/c.441GT; c.621C>G/c.707GC) in CHIP gene in two additional kindreds. These mutations co-segregated exactly with the disease in these families and were not observed in 500 control subjects with matched ancestry. CHIP colocalized with NR2A, a subunit of the N-methyl-D-aspartate receptor, in the cerebellum, pons, medulla oblongata, hippocampus and cerebral cortex. Wild-type, but not disease-associated mutant CHIPs promoted the degradation of NR2A, which may underlie the pathogenesis of ataxia. In conclusion, using a combination of whole-exome sequencing and linkage analysis, we identified CHIP, encoding a U-box containing ubiquitin E3 ligase, as a novel causative gene for autosomal recessive cerebellar ataxia.


The direct calculation of parametric images from dynamic PET data using maximum-likelihood iterative reconstruction.
The aim of this work is to calculate, directly from projection data, concise images characterizing the spatial and temporal distribution of labelled compounds from dynamic PET data. Conventionally, image reconstruction and the calculation of parametric images are performed sequentially. By combining the two processes, low-noise parametric images are obtained, using a computationally feasible parametric iterative reconstruction (PIR) algorithm. PIR is performed by restricting the pixel time-activity curves to a positive linear sum of predefined time characteristics. The weights in this sum are then calculated directly from the PET projection data, using an iterative algorithm based on a maximum-likelihood iterative algorithm commonly used for tomographic reconstruction. The ability of the algorithm to extract known kinetic components from the raw data is assessed, using data from both a phantom experiment and clinical studies. The calculated parametric images indicate differential kinetic behaviour and have been used to aid in the identification of tissues which exhibit differences in the handling of labelled compounds. These parametric images should be helpful in defining regions of interest with similar functional behaviour, and with FDG Patlak analysis.


Polydnavirus Innexins Disrupt Host Cellular Encapsulation and Larval Maturation.
Polydnaviruses are dsDNA viruses associated with endoparasitoid wasps. Delivery of the virus during parasitization of a caterpillar and subsequent virus gene expression is required for production of an amenable environment for parasitoid offspring development. Consequently, understanding of Polydnavirus gene function provides insight into mechanisms of host susceptibility and parasitoid wasp host range. Polydnavirus genes predominantly are arranged in multimember gene families, one of which is the vinnexins, which are virus homologues of insect gap junction genes, the innexins. Previous studies of Campoletis sonorensis Ichnovirus Vinnexins using various heterologous systems have suggested the four encoded members may provide different functionality in the infected caterpillar host. Here, we expressed two of the members, vnxG and vnxQ2, using recombinant baculoviruses in susceptible host, the caterpillar Heliothis virescens. Following intrahemocoelic injections, we observed that >90% of hemocytes (blood cells) were infected, producing recombinant protein. Larvae infected with a vinnexin-recombinant baculovirus exhibited significantly reduced molting rates relative to larvae infected with a control recombinant baculovirus and mock-infected larvae. Similarly, larvae infected with vinnexin-recombinant baculoviruses were less likely to survive relative to controls and showed reduced ability to encapsulate chromatography beads in an immune assay. In most assays, the VnxG protein was associated with more severe pathology than VnxQ2. Our findings support a role for Vinnexins in CsIV and more broadly Ichnovirus pathology in infected lepidopteran hosts, particularly in disrupting multicellular developmental and immune physiology.


Examination of gas exchange and blood lactate thresholds in Paralympic athletes during upper-body poling.
The primary aim was to compare physiological and perceptual outcome parameters identified at common gas exchange and blood lactate (BLa) thresholds in Paralympic athletes while upper-body poling. The secondary aim was to compare the fit of the breakpoint models used to identify thresholds in the gas exchange thresholds data versus continuous linear and curvilinear (no-breakpoint) models. Fifteen elite Para ice hockey players performed seven to eight 5-min stages at increasing workload until exhaustion during upper-body poling. Two regression lines were fitted to the oxygen uptake (VO2)-carbon dioxide (VCO2) and minute ventilation (VE)/VO2 data to determine the ventilatory threshold (VT), and to the VCO2-VE and VE/VCO2 data to determine the respiratory compensation threshold (RCT). The first lactate threshold (LT1) was determined by the first rise in BLa (+0.4mmol·L-1 and +1.0mmol·L-1) and a breakpoint in the log-log transformed VO2-BLa data, and the second lactate threshold (LT2) by a fixed rise in BLa above 4mmol·L-1 and by employing the modified Dmax method. Paired-samples t-tests were used to compare the outcome parameters within and between the different threshold methods. The fit of the two regression lines (breakpoint model) used to identify thresholds in the gas exchange data was compared to that of a single regression line, an exponential and a 3rd order polynomial curve (no-breakpoint models) by Akaike weights. All outcome parameters identified with the VT (i.e., breakpoints in the VO2-VCO2 or VE/VO2 data) were significantly higher than the ones identified with a fixed rise in BLa (+0.4 or +1.0mmol·L-1) at the LT1 (e.g. BLa: 5.1±2.2 or 4.9±1.8 vs 1.9±0.6 or 2.3±0.5mmol·L-1,p<0.001), but were not significantly different from the log-log transformed VO2-BLa data (4.3±1.6mmol·L-1,p>0.06). The outcome parameters identified with breakpoints in the VCO2-VE data to determine the RCT (e.g. BLa: 5.5±1.4mmol·L-1) were not different from the ones identified with the modified Dmax method at the LT2 (5.5±1.1mmol·L-1) (all p>0.53), but were higher compared to parameters identified with VE/VCO2 method (4.9±1.5mmol·L-1) and a fixed BLa value of 4mmol·L-1 (all p<0.03). Although we were able to determine the VT and RCT via different gas exchange threshold methods with good fit in all 15 participants (mean R2>0.931), the continuous no-breakpoint models had the highest probability (>68%) of being the best models for the VO2-VCO2 and the VCO2-VE data. In Paralympic athletes who exercise in the upper-body poling mode, the outcome parameters identified at the VT and the ones identified with fixed methods at the LT1 showed large differences, demonstrating that these cannot be used interchangeably to estimate the aerobic threshold. In addition, the close location of the VT, RCT and LT2 does not allow us to distinguish the aerobic and anaerobic threshold, indicating the presence of only one threshold in athletes with a disability exercising in an upper-body mode. Furthermore, the better fit of continuous no-breakpoint models indicates no presence of clear breakpoints in the gas exchange data for most participants. This makes us question if breakpoints in the gas exchange data really exist in an upper-body exercise mode in athletes with disabilities.


Restraint-induced thermogenesis blunted by fasting in rats.
Physical restraint was performed in fasted (F3, fasted for 3 days; F7, fasted for 7 days), and fed control (C) rats. In contrast to the C group, the F3 and F7 groups showed a low resting metabolism and a low calorigenic response to restraint. During restraint, plasma levels of norepinephrine (NE) and epinephrine (E) were markedly increased but were not significantly different between the C and F7 groups. Calorigenic responses to NE and E (6.0 and 12.0 nmol X kg-1 X min-1) were significantly less in the F3 and F7 groups than in the C group. Plasma concentrations of glucose were increased by the infusion of catecholamines in the C and F7 groups. The values were not different between the two groups. Plasma levels of free fatty acid in the F7 group were significantly higher than in the C group before and during catecholamine infusion. Plasma concentrations of thyroxine and triiodothyronine were significantly less in the F7 group than in the C group. The blunted restraint-induced thermogenesis in fasted rats may be mainly attributed to the decreased calorigenic response to catecholamines. The decreased calorigenic response may be due to suppressed utilization of energy substrates in calorigenic tissues produced by the lowered activity of thyroid hormone.


Cholesterol homeostasis in cardiovascular disease and recent advances in measuring cholesterol signatures.
Despite the biochemical importance of cholesterol, its abnormal metabolism has serious cellular consequences that lead to endocrine disorders such as cardiovascular disease (CVD). Nevertheless, the impact of blood cholesterol as a CVD risk factor is still debated, and treatment with cholesterol-lowering drugs remains controversial, particularly in older patients. Although, the prevalence of CVD increases with age, the underlying mechanisms for this phenomenon are not well understood, and metabolic changes have not been confirmed as predisposing factors of atherogenesis. The quantification of circulating biomarkers for cholesterol homeostasis is therefore warranted, and reference values for cholesterol absorption and synthesis should be determined in order to establish CVD risk factors. The traditional lipid profile is often derived rather than directly measured and lacks a universal standard to interpret the results. In contrast, mass spectrometry-based cholesterol profiling can accurately measure free cholesterol as a biologically active component. This approach allows to detect alterations in various metabolic pathways that control cholesterol homeostasis, by quantitative analysis of cholesterol and its precursors/metabolites as well as dietary sterols. An overview of the mechanism of cholesterol homeostasis under different physiological conditions may help to identify predictive biomarkers of concomitant atherosclerosis and conventional CVD risk factors.


SARS-CoV-2 RNA in Wastewater Settled Solids Is Associated with COVID-19 Cases in a Large Urban Sewershed.
Wastewater-based epidemiology may be useful for informing public health response to viral diseases like COVID-19 caused by SARS-CoV-2. We quantified SARS-CoV-2 RNA in wastewater influent and primary settled solids in two wastewater treatment plants to inform the preanalytical and analytical approaches and to assess whether influent or solids harbored more viral targets. The primary settled solids samples resulted in higher SARS-CoV-2 detection frequencies than the corresponding influent samples. Likewise, SARS-CoV-2 RNA was more readily detected in solids using one-step digital droplet (dd)RT-PCR than with two-step RT-QPCR and two-step ddRT-PCR, likely owing to reduced inhibition with the one-step ddRT-PCR assay. We subsequently analyzed a longitudinal time series of 89 settled solids samples from a single plant for SARS-CoV-2 RNA as well as coronavirus recovery (bovine coronavirus) and fecal strength (pepper mild mottle virus) controls. SARS-CoV-2 RNA targets N1 and N2 concentrations correlated positively and significantly with COVID-19 clinically confirmed case counts in the sewershed. Together, the results demonstrate that measuring SARS-CoV-2 RNA concentrations in settled solids may be a more sensitive approach than measuring SARS-CoV-2 in influent.


Cerebral tuberculoma mimicking high grade glial tumor.
Tuberculosis has been an important public health problem in both developing and develop nations. Tuberculosis of the central nervous system is rare. Tuberculosis meningitis and tuberculoma are the two most important manifestations of tuberculosis of the CNS. Intracranial tuberculomas may be solitary or multiple. Solitary tuberculomas may be indistinguishable from cranial abscess or primary brain tumor. It is necessary to rule out tuberculoma in patients with intracranial mass lesions. We present a case of tuberculoma mimicking a high grade glial tumor on magnetic resonance imaging and clinical presentation. A 30-year-old woman presented with one-month history of epilepsy. Cranial magnetic resonance imaging showed a left occipital peripheral ring-enhanced lesion with central necrosis. There was a strong suspicion of glial tumor. The lesion was totally excised with left occipital craniotomy. Histological examination of mass revealed a tuberculoma. The patient was treated with antituberculous chemotherapy.


Using remote sensing to map larval and adult populations of Anopheles hyrcanus (Diptera: Culicidae) a potential malaria vector in Southern France.
Although malaria disappeared from southern France more than 60 years ago, suspicions of recent autochthonous transmission in the French Mediterranean coast support the idea that the area could still be subject to malaria transmission. The main potential vector of malaria in the Camargue area, the largest river delta in southern France, is the mosquito Anopheles hyrcanus (Diptera: Culicidae). In the context of recent climatic and landscape changes, the evaluation of the risk of emergence or re-emergence of such a major disease is of great importance in Europe. When assessing the risk of emergence of vector-borne diseases, it is crucial to be able to characterize the arthropod vector's spatial distribution. Given that remote sensing techniques can describe some of the environmental parameters which drive this distribution, satellite imagery or aerial photographs could be used for vector mapping. In this study, we propose a method to map larval and adult populations of An. hyrcanus based on environmental indices derived from high spatial resolution imagery. The analysis of the link between entomological field data on An. hyrcanus larvae and environmental indices (biotopes, distance to the nearest main productive breeding sites of this species i.e., rice fields) led to the definition of a larval index, defined as the probability of observing An. hyrcanus larvae in a given site at least once over a year. Independent accuracy assessments showed a good agreement between observed and predicted values (sensitivity and specificity of the logistic regression model being 0.76 and 0.78, respectively). An adult index was derived from the larval index by averaging the larval index within a buffer around the trap location. This index was highly correlated with observed adult abundance values (Pearson r = 0.97, p < 0.05). This allowed us to generate predictive maps of An. hyrcanus larval and adult populations from the landscape indices. This work shows that it is possible to use high resolution satellite imagery to map malaria vector spatial distribution. It also confirms the potential of remote sensing to help target risk areas, and constitutes a first essential step in assessing the risk of re-emergence of malaria in southern France.


Pathway for post-prostatectomy urinary incontinence: impact on patient confidence and satisfaction.
Between 8% and 87% of prostatectomies result in urinary incontinence, with around half of patients using incontinence pads daily at 6 months. Specialist urology continence nurses at the Norfolk and Norwich University Hospitals NHS Foundation Trust created a pre- and post-surgical care pathway formalising support for these patients, which involves the provision of TENA Men (Essity) male incontinence pads. This audit aimed to assess patient satisfaction with this pathway and TENA Men pads. Patients who underwent a radical prostatectomy at NNUH between 27 April and 9 November 2021 and who required continence pads were invited to fill out an online anonymous mixed-method (mainly qualitative) survey. Of 28 respondents, 71% reported incontinence after their surgical catheter was removed. Most (89%) were satisfied with the preoperative advice. Of 19 respondents to questions on confidence and satisfaction, 16 were confident that the pads they had been prescribed were helping them to manage urinary leakage, and 16 were confident or very confident that they could manage their incontinence themselves. Generally, respondents were confident that their overall and mental health had improved, and most were confident or very confident that they had less anxiety. However, less than a quarter of respondents were 'very confident' about going out, meeting people or exercising. All but one respondent found TENA Men pads easy to fit, and the most used words in the free-text explanations of what they most included 'easy', 'discreet', 'comfortable' and 'unobtrusive'. The clinical pathway helped give patients undergoing radical prostatectomy confidence in their ability to manage post-surgery incontinence themselves and could be of value in other hospitals. Easy access to incontinence pads designed for the male anatomy has an important part in this.


A randomized pilot trial of a couple-based intervention addressing sexual concerns for breast cancer survivors.
The purpose was to test the feasibility, acceptability, and preliminary efficacy of a 4-session couple-based Intimacy Enhancement (IE) intervention addressing breast cancer survivors' sexual concerns delivered via telephone. Twenty-nine post-treatment breast cancer survivors reporting sexual concerns and their intimate partners were randomized (2:1) to the IE intervention or to an educational control condition, both of which were delivered by trained psychosocial providers. Feasibility and acceptability were measured through recruitment, retention, session completion, and post-intervention program evaluations. Couples completed validated sexual, relationship, and psychosocial outcome measures at pre- and post-intervention. Between-group effect sizes and 95% confidence intervals were calculated using the Hedges g. Data supported intervention feasibility and acceptability. For survivors, the IE intervention had medium to large positive effects on all sexual outcomes and most psychosocial outcomes. Effects were less visible for relationship outcomes and were similar but somewhat smaller for partners. The IE intervention demonstrated feasibility, acceptability, and promise in addressing breast cancer survivors' sexual concerns and enhancing their and their partners' intimate relationships and psychosocial well-being. Implications for Psychosocial Oncology Practice The IE intervention demonstrated feasibility and acceptability, suggesting it could be well-received by breast cancer survivors with sexual concerns and their partners. Effects of the IE intervention on breast cancer survivors' sexual concerns and on their and their partners' intimate relationships and psychosocial well-being could not be attributed to therapist time and attention. Interventions that psychosocial providers can use to address breast cancer survivors' sexual concerns are important to the growing number of breast cancer survivors living for many years after their diagnosis.


Biochar from commercially cultivated seaweed for soil amelioration.
Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum--brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma--red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.


Production and characterization of bioactive peptides in novel functional soybean chhurpi produced using Lactobacillus delbrueckii WS4.
A novel soy chhurpi product was developed by fermentation of soymilk using proteolytic Lactobacillus delbrueckii strains isolated from traditional chhurpi production of Sikkim Himalaya. Soymilk fermentation by L. delbrueckii WS4 was associated with the hydrolysis of globulin proteins, with observed antioxidant, and ACE-inhibitory activity which further increased upon simulated in vitro gastrointestinal digestion. Peptidomics analysis of soy chhurpi and its gastrointestinal digest resulted in the identification of bioactive peptides with ACE-inhibitory and antioxidant properties. In silico antihypertensive property prediction followed by molecular docking study demonstrated strong binding affinity of selected peptides with ACE. The glycinin-derived peptide, SVIKPPTDE escaped gastrointestinal digestion and demonstrated strong non-bond interactions with ACE catalytic residues. QSAR models predicted an ACE-inhibitory IC50 of 21.29 µM for SVIKPPTDE. This is the first report on the production of novel functional soy chhurpi cheese using defined starter strains and the identification of bioactive peptides in undigested and gastrointestinal digested soy chhurpi.