Effect of human milk and other neonatal variables on lung function at three months corrected age.
To evaluate the impact of human milk and different neonatal variables on tidal breathing flow-volume loop (TBFVL) parameters within three months' corrected age (CA) in infants born ≤32 wks or weighing <1500 g. We retrospectively studied 121 infants with gestational age (GA) ≤ 32 weeks or birth weight (BW) <1500 gr who had lung function assessment within three months' CA by TBFVL analysis between June 2009 and April 2018. We investigated the impact of GA, gender, being Small for GA (SGA), sepsis, days of mechanical ventilation (MV) and human milk feeding (HMF) on later respiratory function, both in the entire group and according to BW ( ≤1000 g and >1000 g). The mean(SD) z-score for tidal volume (Vt) and time to peak expiratory flow to expiratory time (tPTEF/tE) were respectively -4.3 (2.5) and -0.8 (2.0) for the overall population with no significant differences between infants <1000 g or ≥1000 g. The mean(SD) Vt standardized for body weight was 6.2(2.0) ml/kg. Being female was associated with better Vt/Kg, whereas longer MV or being born SGA were associated with worst tPTEF/tE. For infants with BW < 1000 gr, tPTEF/tE was positively associated with HMF. An early TBFVL assessment within three months' CA already reveals lung function alteration in preterm infants. Being female is associated with better Vt/Kg, while longer duration of MV or being born SGA negatively affect tPTEF/tE. The positive association between HMF and better tPTEF/tE in infants with BW <1000 g has emerged, which deserves further investigation.


A Human Lin- CD123+ CD127low Population Endowed with ILC Features and Migratory Capabilities Contributes to Immunopathological Hallmarks of Psoriasis.
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127- ILC populations and an early ILC precursor (EILP) CD127low. ILC development has predominately been investigated in mouse models. However, in humans, different transcription factors have been described for ILC identification. NFIL3 (nuclear factor, IL-3 regulated) is crucial for ILC development in response to IL-7. CD123 (IL-3Rα) is usually used to exclude basophils during ILC identification, however, it is unknown if in response to IL-3, NFIL3 could be relevant to induce ILC features in Lin- CD123+ populations in addition, is also unknown whether peripheral blood (PB) population with ILC features may have skin-homing potential to participate in skin inflammatory chronic diseases. Here, we report a Lin- CD123+ CD127low CD7+ CLA+ population that share some phenotypic properties with basophils, but expresses several transcription factors for ILC commitment such as inhibitor of DNA binding 2 (Id2), NFIL3, promyelocytic leukemia zinc finger (PLZF), thymocyte selection-associated high-mobility group box protein (TOX), and T cell factor-1 (TCF-1). In addition, this population expresses different ILC markers: CD132, CD90, CD161, α4 integrin, c-Kit, CRTH2, AhR, and IL-23R. IL-3 prevents apoptosis and increases their NFIL3, TOX, and PLZF expression. In PB, the CD123+ CD127low population is predominantly a conspicuous population that expresses T-bet and RORγt. The Lin- CD123+ CD127low population in PB has a limited Th type cytokine expression and highly expresses IL-8. The Lin- CD123+ CD127low population expresses skin-homing receptors (cutaneous lymphocyte antigen and CXCR4) and transmigrates through endothelial cells in response to SDF-1. An equivalent Lin- CD123low population was identified in control skin, which shows a broader phenotypic diversity and cytokine production, including IL-22 and IL-17. Remarkably, the CD123low population in the lesion and non-lesion skin of psoriasis patients expresses IL-17 and IL-22. Our findings suggest the identification of an alternative Lin- CD123+ CD127low population with ILC features endowed with migratory capabilities that might contribute to immunopathological hallmarks of psoriasis.


The Parental Bonding Instrument: A psychometric measure to assess parenting practices in the homes in Bangladesh.
There is growing importance of the Parental Bonding Instrument (PBI) in clinical practice and research on parenting and parental bonding. Since the development of this diagnostic tool (Parker et al., Brit. J. Med. Psycho.1979; 52:1-10), a number of validation studies have been done in various cultures. The aim of the present study was to translate the measure into Bangla and validate in Bangladeshi culture. A total of 200 adolescents participated in the study. Exploratory factor analysis (EFA) of the data from 191 participants (who provided complete responses) identified a two-factor (Care and Overprotection) structure of the PBI with 17 items. The two factors together explained 44.18% of the total variance. The factors showed moderate to very high internal consistency (Cronbach's α=0.863 for Care; 0.622 for Overprotection), and very strong convergent and discriminant validity as evident by their correlations with the measures of cognitive distortions and antisocial behaviors. In line with the original tool we defined four types of parenting style, such as Affectionate constraint, Affectionless control, Optimal parenting, and Neglectful parenting. This study opens the door of future research on parenting practices and parent-child relationships in Bangladesh.


Deciphering the structural and functional impact of missense mutations in Egr1-DNA interacting interface: an integrative computational approach.
Early growth response-1 (Egr1) is a zinc-finger transcription factor that plays a critical role in controlling cell growth, proliferation, differentiation, angiogenesis, and apoptosis. Egr1 is induced by many growth factors, cytokines, and stress signals and is also known to be involved in several pathological conditions like cancer, neurological and ocular disorders. The DNA binding domain of Egr1 is a highly conserved Cys2His2 (C2H2) zinc finger (ZNF) domain which specifically binds to GC-rich consensus sequence GcG (G/T) GGGCG and activates transcription. As the C2H2 domain specifically recognizes its DNA target, the mutations spanning this region shall perturb DNA recognition and may hinder transcription of target genes. Therefore, in this study, the missense mutations occurring specifically at the DNA binding domain (DBD) of Egr1 were probed by computational approaches involving in silico screening of pathogenic and functional mutants coupled with extensive molecular dynamics simulations, to determine the mutants that affect its structural stability and interactions with DNA. From the pathogenicity analysis of 38 missense mutations spanning Egr1-DBD, 17 were predicted as pathogenic, and 7 amongst these were found to have functional impact on Egr1. On combined analysis of molecular dynamics simulation, Residue interaction analysis and Egr1-DNA interaction analysis results, the mutants R371C and R375C showed least impact, whilst, H382R tend to increase the structural stability, whereas R360H, H390R, E393V, and H414Y conferred greater impact by altering the structural stability and DNA interactions. Hence, this study exposes the prospects of considering these 4 deleterious mutations for clinical significance, but needs further experimental validation.HighlightsEgr1's DNA binding domain is a highly conserved Cys2His2 (C2H2) zinc finger domain that specifically recognizes its DNA target.Mutations spanning in the DNA binding domain shall perturb DNA recognition and may hinder transcription.Among the missense mutations, mutants R360H, H390R, E393V, and H414Y were inferred to have a greater impact on Egr1 by altering the structural stability and DNA interactions.


Cholesterol gallstone disease: the current status of nonsurgical therapy.
Gallstone disease is a common disease that appears to be related to a Western diet. The underlying pathogenesis is a subtle alteration in the liver such that excessive cholesterol is extracted from the liver cell by bile acids undergoing an enterohepatic recirculation. Gallstone disease progresses through well-defined stages, beginning with a bile supersaturated with cholesterol and proceeding to crystal formation, stone growth, and finally symptoms caused by impaction of a stone in either the cystic duct or the common bile duct. The natural history is that most stones never cause symptoms. Stones that cause symptoms have been present for an average of 12 years. The treatment of truly asymptomatic stones should be observation. Ultrasonography of the right upper quadrant is the gold standard for the diagnosis of stones in the gallbladder. Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for the diagnosis of stones in the common bile duct. Oral cholecystogram (OCG) helps select patients who have noncalcified, floating stones that may be dissolved with bile acids or methyl tertiary butyl ether (MTBE). Therapy with chenodiol has been a disappointment because of a low complete response rate. The ideal candidate for attempted dissolution with chenodiol would be a thin woman with hypercholesterolemia and a small number of symptomatic, small, floating, radiolucent gallstones. Ursodeoxycholic acid (Urso), when it is available, will have all of the attributes of chenodiol and virtually none of the side effects. Rapid dissolution of gallstones with MTBE shows great promise of being a generally available means of dissolving gallstones. Extracorporeal shock wave lithotripsy also shows promise, but its general availability may be limited by the cost of the equipment needed. As of now, the treatment of choice for symptomatic gallstones remains cholecystectomy, unless there is a compelling reason not to operate.


Caregiver experiences of hospice dementia care: a systematic review and meta-ethnography.
Hospices are regarded as gold standard providers of end-of-life care. The term hospice, however, is broadly used, and can describe a type of care offered in a variety of health care services (e.g. nursing homes). It thus becomes complex for families to decide between services. We aimed to review the evidence around the experience of family carers of people with dementia accessing in-patient hospice settings for end-of-life care. We registered the review protocol on PROSPERO. We used PerSPE(C)TiF to systematically organise our search strategy. The evidence was reviewed across six databases: PubMed, EMBASE, PsycINFO, ASSIA, ISI Web, and CINAHL. We used meta-ethnography as per the eMERGe guidance for data interpretation. Four studies were included. Two third-order constructs were generated through meta-ethnography: expectations of care and barriers to quality of care. We found that carers had expectations of care, and these could change over time. If discussion was not held with hospice staff early on, the carers could experience reduced care quality due to unmatched expectations. Unmatched expectations acted as barriers to care and these were found in terms of carers not feeling adequately supported, and/or having the person discharged from hospice, which would entail increased care responsibility for carers. In view of an increase in new dementia cases over time and with hospice services being under pressure, integrating palliative care services within community-based models of care is key to reducing the risk of having inadequate and under resourced services for people with dementia.


Epithelial and non-epithelial Ptch1 play opposing roles to regulate proliferation and morphogenesis of the mouse mammary gland.
Patched 1 (Ptch1) has epithelial, stromal and systemic roles in murine mammary gland organogenesis, yet specific functions remain undefined. Cre-recombinase-mediated Ptch1 ablation in mammary epithelium increased proliferation and branching, but did not phenocopy transgenic expression of activated smoothened (SmoM2). The epithelium showed no evidence of canonical hedgehog signaling, and hyperproliferation was not blocked by smoothened (SMO) inhibition, suggesting a non-canonical function of PTCH1. Consistent with this possibility, nuclear localization of cyclin B1 was increased. In non-epithelial cells, heterozygous Fsp-Cre-mediated Ptch1 ablation increased proliferation and branching, with dysplastic terminal end buds (TEB) and ducts. By contrast, homozygous Ptch1 ablation decreased proliferation and branching, producing stunted ducts filled with luminal cells showing altered ovarian hormone receptor expression. Whole-gland transplantation into wild-type hosts or estrogen/progesterone treatment rescued outgrowth and hormone receptor expression, but not the histological changes. Bone marrow transplantation failed to rescue outgrowth. Ducts of Fsp-Cre;Ptch1fl/fl mice were similar to Fsp-Cre;SmoM2 ducts, but Fsp-Cre;SmoM2 outgrowths were not stunted, suggesting that the histology might be mediated by Smo in the local stroma, with systemic Ptch1 required for ductal outgrowth and proper hormone receptor expression in the mammary epithelium.


Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice.
Acute promyelocytic leukemia (APL) is associated with reciprocal chromosomal translocations involving the retinoic acid receptor alpha (RARalpha) locus on chromosome 17. In the majority of cases, RARalpha translocates and fuses with the promyelocytic leukemia (PML) gene located on chromosome 15. The resulting fusion genes encode the two structurally unique PML/RARalpha and RARalpha/PML fusion proteins as well as aberrant PML gene products, the respective pathogenetic roles of which have not been elucidated. We have generated transgenic mice in which the PML/RARalpha fusion protein is specifically expressed in the myeloid-promyelocytic lineage. During their first year of life, all the PML/RARalpha transgenic mice have an abnormal hematopoiesis that can best be described as a myeloproliferative disorder. Between 12 and 14 months of age, 10% of them develop a form of acute leukemia with a differentiation block at the promyelocytic stage that closely mimics human APL even in its response to retinoic acid. Our results are conclusive in vivo evidence that PML/RARalpha plays a crucial role in the pathogenesis of APL.


Semiology of Tremors.
Since the description by Galen in the 2nd Century, A.D., clinical neurology has acknowledged the existence of two types of tremor: that which occurs at rest and that occuring during the execution of movement. With the help of refined methods of analysis, E.M.G. and cinephotography, the authors have carried out a detailed clinical assessment in more than 400 patients. The basic criterion used to define a tremor was the classical definition of Dejerine: "An involuntary, rhythmical and symmetrical movement about an axis of equilibrium." As a result of this study, the conclusion has been reached that there are two types of tremor: postural tremor and tremor of attitude. Both are present while the limb remains immobile, whether by wilful design or when at rest in a position of posture and subject only to the action of gravity. During voluntary movement, tremor is not present. Irregular, asymmetrical and non-rhythmic oscillations may appear however - as in so-called intention tremor, of cerebellar origin - but this abnormal movement can hardly be called a real tremor. It is merely a manifestation of ataxia. As a consequence of this study, it is suggested that further understanding of the basic mechanism of tremor can be reached by the investigation of the central neural structures which are involved in the physiology of posture and attitude.


Targeted Oral Naltrexone for Mild to Moderate Alcohol Use Disorder Among Sexual and Gender Minority Men: A Randomized Trial.
The authors sought to determine the efficacy of targeted naltrexone in sexual and gender minority men (SGM) who binge drink and have mild to moderate alcohol use disorder. In a double-blind placebo-controlled trial, a total of 120 SGM who binge drink and have mild to moderate alcohol use disorder were randomized in a 1:1 ratio to receive targeted oral naltrexone (50 mg) or placebo with weekly counseling for 12 weeks. The study's primary endpoints were binge-drinking intensity, defined as 1) number of drinks in the past 30 days; 2) any binge drinking in the past week; 3) number of binge-drinking days in the past week; and 4) number of drinking days in the past week. The study also measured changes in alcohol use with two alcohol biomarker measures: ethyl glucuronide in urine samples and phosphatidylethanol (PEth) in dried blood spot samples. Ninety-three percent completed the trial, with 85% of weekly follow-up visits completed. In intention-to-treat analyses, naltrexone was associated with a significantly reduced reported number of binge-drinking days (incidence rate ratio [IRR]=0.74, 95% CI=0.56, 0.98; number needed to treat [NNT]=2), weeks with any binge drinking (IRR=0.83, 95% CI=0.72, 0.96; NNT=7.4), number of drinks per month (IRR=0.69, 95% CI=0.52, 0.91; NNT=5.7 for 10 drinks), and alcohol craving scores (coefficient=-9.25, 95% CI=-17.20, -1.31). In as-treated analyses among those who took their medication on average at least 2.5 days per week (the median frequency in the study), naltrexone reduced any binge drinking (IRR=0.84, 95% CI=0.71, 0.99), number of binge-drinking days (IRR=0.67, 95% CI=0.47, 0.96), and PEth concentrations (coefficient=-55.47, 95% CI=-110.75, -0.20). At 6 months posttreatment, naltrexone had sustained effects in number of drinks per month (IRR=0.69, 95% CI=0.50, 0.97), number of binge-drinking days (IRR=0.67, 95% CI=0.47, 0.95), and any binge drinking in the past week (IRR=0.79, 95% CI=0.63, 0.99). Targeted naltrexone significantly reduced drinking outcomes among SGM with mild to moderate alcohol use disorder during treatment, with sustained effects at 6 months posttreatment. Naltrexone may be an important pharmacotherapy to address binge drinking in populations with mild to moderate alcohol use disorder.


Endotoxemia predicts outcome in acute pancreatitis.
The incidence of complications of acute pancreatitis is high in patients with endotoxemia, and so we determined the endotoxin levels in the blood and peritoneal fluid of patients with acute severe pancreatitis to correlate the levels with any sequelae. Fourteen patients with acute severe pancreatitis were examined with regard to clinical features, biochemical tests, and laparotomy (n = 9). In all coagulation profiles, blood gas analysis, chest and abdominal x-rays, ultrasound, and abdominal computed tomography scan (n = 10) were performed. Qualitative estimation of endotoxin levels was done in peripheral blood and peritoneal and peripancreatic fluid. Ten (71.42%) of 14 patients had endotoxin in the blood, and 9 (64.28%) had it in the peritoneal fluid. Twelve (85.7%) had pulmonary involvement, with hypoxia being the most common (85.7%); among them endotoxin was found in the blood of 10 (83.32%) and in the peritoneal fluid of 8 (66.66%) patients. Renal dysfunction was found in 4 (28.57%) patients; endotoxin was present in the blood of all 4 patients and in the peritoneal fluid of 3 (75%) patients. Cardiovascular abnormality was detected in 8 (57.14%) patients, and endotoxin was present in the blood and peritoneal fluid of all patients. Metabolic abnormality was present in 8 (57.14%) patients; endotoxin was present in the blood of all 8 patients and in the peritoneal fluid of 7 (87.6%) patients. Eight (88.88%) of the 9 patients who required surgery had endotoxemia. Three (30%) patients with endotoxemia survived, whereas all 4 patients without endotoxemia survived. Mean hospital stay was 61.2 days and 46.7 days for endotoxin-positive and endotoxin-negative patients, respectively. We conclude that the presence of endotoxin in blood and peritoneal fluid correlates with the severity, systemic complications, and mortality rates of acute pancreatitis. Endotoxin estimation can identify patients at risk in the early stages of acute pancreatitis.


Histocompatibility and T-B cell cooperation in mouse radiation chimeras.
Cooperative interaction between histocompatible as well as histoincompatible T and B cells in vivo was studied with B cell-bearing syngeneic radiation chimeras receiving syngeneic, semiallogeneic, or allogeneic A and T cells in various combinations. The results indicated the following: i) Histoincompatible T and B cells normally did not cooperate successfully for generation of antibody-forming cells. ii) Semiallogeneic (C3BF1) T cells cooperated successfully with parent-type (C3H) B cells developed in parent-type syngeneic chimeras (C3H/C3H), whereas parent-type (C3H as well as C57BL) T cells failed to cooperate with F1 (BC3F1) B cells developed in F1 syngeneic chimeras (BC3F1/BC3F1). iii) T cells obtained from C57BL/C3H or C57BL/C3BF1 chimeras, which were most likely donor (C57BL)- derived, cooperated successfully with C3H-derived B cells developed in C3H/C3H chimeras. iv) Evidence was obtained suggesting that stimulation of antibody response by allogeneic effect in the absence of syngeneic or semisyngeneic helper T cells did not take place in this experimental system. v) With the use of congenic resistant strains, it was shown that alloantigens controlled by H-2 loci, in particular by the K-I region of this gene complex, constituted the barrier of cooperative interaction between histoincompatible T and B cells. vi) Cooperation between H-2 compatible, non-syngeneic T and B cells was also disturbed in varying degrees depending on the strain combinations, thus indicating that cell surface antigens controlled by non-H-2 loci also had a significant role for the cooperative interaction between T and B cells. Problems associated with these findings were discussed.


Immune Modulation by Volatile Anesthetics.
Volatile general anesthetics continue to be an important part of clinical anesthesia worldwide. The impact of volatile anesthetics on the immune system has been investigated at both mechanistic and clinical levels, but previous studies have returned conflicting findings due to varied protocols, experimental environments, and subject species. While many of these studies have focused on the immunosuppressive effects of volatile anesthetics, compelling evidence also exists for immunoactivation. Depending on the clinical conditions, immunosuppression and activation due to volatile anesthetics can be either detrimental or beneficial. This review provides a balanced perspective on the anesthetic modulation of innate and adaptive immune responses as well as indirect effectors of immunity. Potential mechanisms of immunomodulation by volatile anesthetics are also discussed. A clearer understanding of these issues will pave the way for clinical guidelines that better account for the impact of volatile anesthetics on the immune system, with the ultimate goal of improving perioperative management.


Can diet prevent nonmelanoma skin cancer progression?
Nonmelanoma skin cancer is the most prevalent malignant disease among light-skinned individuals in the USA, accounting for approximately 1 million new cases annually. Solar ultraviolet radiation is known to be the major cause of skin cancer. The idea that diet, particularly dietary fat, may play a role in modulating cancer incidence has been based largely upon indirect epidemiologic evidence. However, few studies have found correlations of dietary fat intake with skin cancer incidence. Nevertheless, a large body of evidence with experimental animals and one clinical intervention trial, the latter avoiding the pitfalls of many epidemiologic investigations, clearly demonstrate that the level of dietary fat intake can have a significant influence on the occurrence of skin cancer in individuals at high risk.


Frequency-dependent tACS modulation of BOLD signal during rhythmic visual stimulation.
Transcranial alternating current stimulation (tACS) has emerged as a promising tool for modulating cortical oscillations. In previous electroencephalogram (EEG) studies, tACS has been found to modulate brain oscillatory activity in a frequency-specific manner. However, the spatial distribution and hemodynamic response for this modulation remains poorly understood. Functional magnetic resonance imaging (fMRI) has the advantage of measuring neuronal activity in regions not only below the tACS electrodes but also across the whole brain with high spatial resolution. Here, we measured fMRI signal while applying tACS to modulate rhythmic visual activity. During fMRI acquisition, tACS at different frequencies (4, 8, 16, and 32 Hz) was applied along with visual flicker stimulation at 8 and 16 Hz. We analyzed the blood-oxygen-level-dependent (BOLD) signal difference between tACS-ON vs tACS-OFF, and different frequency combinations (e.g., 4 Hz tACS, 8 Hz flicker vs 8 Hz tACS, 8 Hz flicker). We observed significant tACS modulation effects on BOLD responses when the tACS frequency matched the visual flicker frequency or the second harmonic frequency. The main effects were predominantly seen in regions that were activated by the visual task and targeted by the tACS current distribution. These findings bridge different scientific domains of tACS research and demonstrate that fMRI could localize the tACS effect on stimulus-induced brain rhythms, which could lead to a new approach for understanding the high-level cognitive process shaped by the ongoing oscillatory signal.


Impact of amino acid and CP restriction from 20 to 140 kg BW on performance and dynamics in empty body protein and lipid deposition of entire male, castrated and female pigs.
Breeding leaner pigs during the last decades may have changed pig's empty body (EB) composition, a key trait for elaborating feeding recommendations. This research aimed to provide new experimental data on changes in the chemical composition of the EB of pigs from 20 to 140 kg BW. In addition, the impact of a reduction in the dietary CP associated with lower lysine, methionine+cystine, threonine and tryptophan levels was determined. In total, 48 males, castrates and females weighing 20 kg BW were allocated either to a control grower-finisher diet formulated according to current Swiss feeding recommendations, or a low CP grower-finisher diet (80% of control). Feed intake was monitored and pigs were weighed weekly. The chemical composition of EB (blood, hairs and hoofs, offals, bile, carcass) was determined at 20, 40, 60, 80, 100, 120 and 140 kg BW on four pigs per gender and diet (eight pigs per gender at 20 kg). The five fractions were weighed and samples were analysed for dry matter, protein, fat and energy. Nutrient deposition rates and N efficiency were calculated by using the 20 kg BW category as reference. Analysis revealed an accurate feed optimisation for the aforementioned essential amino acids (EAA), whereas digestible isoleucine content in the low CP diet was at 70% of the control diet. Despite similar feed intake, daily gain and feed efficiency were impaired (P<0.01) from 20 to 100 kg BW in the low CP compared with the control pigs. In the same growth period, castrates had the greatest feed intake but, together with females, displayed the lowest (P<0.01) feed efficiency. Protein deposition was reduced (P<0.01) by up to 31% with low CP diet and was lower (P<0.01) in castrates and females than males at 100 kg BW. The greatest fat deposition rates were found with low CP diet and castrates. N efficiency improved (P<0.05) by 10% with the low CP diet from 100 to 140 kg. The males displayed the greatest (P<0.05) N efficiency. These findings suggest that the CP content of finisher II diets could be reduced to 102, 102 and 104 g/kg for females, castrates and males, respectively, without a negative impact on protein deposition or growth. It remains unclear whether the negative effects found in the BW range from 20 to 100 kg on the EB deposition were due to the 20% reduction of the dietary CP and the five limiting EAA or to other EAA via an unbalanced EAA profile.


Nocardial infection of the skin.
This paper describes the relationship between different forms of nocardia infection involving the skin. The best recognized of these conditions are systemic nocardiosis and actinomycetoma due to Nocardia spp. in which the organisms are present in either filamentous or grain form respectively. Attention is drawn to evidence for the existence of a primary cutaneous form of nocardiosis which follows inoculation and in which the organisms grow in filamentous phase. It is not clear whether such cases can progress to mycetoma formation if left untreated, or whether other factors are involved. The clinical and laboratory features of these different clinical varieties of nocardia infection are discussed.


PINK1 kinase catalytic activity is regulated by phosphorylation on serines 228 and 402.
Mutations in the PINK1 gene cause early-onset recessive Parkinson disease. PINK1 is a mitochondrially targeted kinase that regulates multiple aspects of mitochondrial biology, from oxidative phosphorylation to mitochondrial clearance. PINK1 itself is also phosphorylated, and this might be linked to the regulation of its multiple activities. Here we systematically analyze four previously identified phosphorylation sites in PINK1 for their role in autophosphorylation, substrate phosphorylation, and mitophagy. Our data indicate that two of these sites, Ser-228 and Ser-402, are autophosphorylated on truncated PINK1 but not on full-length PINK1, suggesting that the N terminus has an inhibitory effect on phosphorylation. We furthermore establish that phosphorylation of these PINK1 residues regulates the phosphorylation of the substrates Parkin and Ubiquitin. Especially Ser-402 phosphorylation appears to be important for PINK1 function because it is involved in Parkin recruitment and the induction of mitophagy. Finally, we identify Thr-313 as a residue that is critical for PINK1 catalytic activity, but, in contrast to previous reports, we find no evidence that this activity is regulated by phosphorylation. These data clarify the regulation of PINK1 through multisite phosphorylation.


[Drowning--characteristic signs and calculation of their diagnostic value].
In a group of 387 drowned subject and 50 controls typical signs of drowning were investigated. Paltaufs spots, aqueous emphysema of the lungs, liquid in the stomach, significant drop of chlorides, creatinine and urea in the left heart and presence of liquid in the paranasal sinuses. The author investigated the frequency of these signs and by comparison of data of these signs in the two groups the diagnostic importance of different diagnostic signs was calculated.


[Bilateral Endogenous Fungal Subretinal Abscesses due to Scedosporium prolificans: a Case Report].
We report a case with bilateral endogenous fungal subretinal abscesses. To our knowledge, this is the first report from Japan in which Scedosporium prolificans (S. prolificans) was cultured from intraocular tissue. A 74-year-old man, receiving chemotherapy for acute myeloid leukemia, complained of visual loss in both eyes. Best-corrected visual acuity was hand motion in the right and 2/200 in the left eye. His right eye showed exophthalmos, inflammation in the anterior chamber and iris neovascularization. Funduscopy revealed no details as there was vitreous opacity in the right eye, and irregular round yellowish-white subretinal lesions involving the macula in the left eye. Blood culture was negative, and C-reactive protein (CRP) and β-D glucan titers were high. An antifungal drug and broad-spectrum antibiotics were initiated. Two days after the initial visit, right visual acuity had deteriorated to light perception. Enucleation of the right eye was performed for diagnosis and treatment. Fungi were cultured from the subretinal lesion, confirming a diagnosis of S. prolificans infection. After systemic administration and intravitreal injections of antifungal agents, the subretinal abscess in the left eye gradually diminished. At present, six months after the first visit, left visual acuity is 20/200. Although S. prolificans endophthalmitis can be intractable, this case suggests that repeated intravitreal antifungal agent injections can be effective.


Associations of pesticides, HCV, HBV, and hepatocellular carcinoma in Egypt.
The rate of hepatocellular carcinoma (HCC) is increasing in Egypt where the major risk factors are chronic infections with hepatitis B and C viruses (HBV and HCV). A major segment of the population is employed in agriculture, raising the possibility that exposure to pesticides is an additional risk factor for HCC. The objective of this study is to investigate pesticides as environmental risk factors for HCC while taking into account viral risk factors. We conducted a case-control study of 236 subjects with confirmed HCC recruited from the National Cancer Institute, Cairo University, Egypt, and 236 controls matched on sex, age group and urban-rural status recruited from orthopedic department, Cairo University Hospital, Egypt. Patients who agreed to participate signed a consent form, answered a questionnaire and gave a blood sample for hepatitis virus testing. The manuals of the Ministry of Agriculture for approved use and type of pesticides since 1965 were linked to the questionnaire data for types of crops and pests that the subject had to combat, to attribute specific pesticides that were used by each subject. Subjects also reported duration of the exposure (years). Case-control comparisons in these data were stratified by sex, age group, and urban vs. rural residence. Data were analyzed using unconditional logistic regression models adjusting for age, HCV RNA, and current hepatitis B infection. Among rural males, the adjusted odds ratio (OR) for organophosphorus compounds was 2.7 (95% CI = 1.3-5.3) and for carbamates it was 2.9 (95% CI = 1.4-5.8). No statistically significant associations between HCC and pesticides were observed for urban males or for females. As expected, the strongest risk factors for HCC in this study were HCV RNA (OR = 16-17) and current HBV infection (OR = 27-28). This study therefore suggests that exposures to organophophorus and carbamate pesticides are additive risk factors to current HCV and HBV infection among rural males. Future investigation should address the possible hepatocarcinogenicity of pesticides using biomarkers of exposure and other techniques to better estimate dose-response relationships.


Estimating screening test sensitivity and tumour progression using tumour size and time since previous screening.
As mammography screening aims to improve the prognosis through earlier detection/treatment, tumour progression and screening test sensitivity (STS) represent key parameters in the evaluation of screening programs. We will here study some methods for estimation of tumour progression and STS, and show how previously used methods can be combined and developed to utilise more of the data available in modern screening programs. Weedon-Fekjaer et al. recently suggested a study design using interview data about time since previous screening to estimate tumour progression and STS in a stepwise Markov model. While useful, the approach does not utilise tumour size measurements, nor link tumour progression to tumour size. Hence, we will here propose formulas for estimating tumour progression and STS using a continuous tumour growth model. To estimate tumour progression and STS, tumour growth curves are followed from one screening to the next, and probabilities for all combinations of tumour sizes at repeated screening examinations calculated. Based on the probabilities for screening detection on subsequent screening examinations, maximum likelihood estimates are calculated. Applied to Norwegian data, the new approach gives similar results to previously published results based on interval data, confirming the earlier estimated large variation in tumour growth rates.


Improved time-varying reproduction numbers using the generation interval for COVID-19.
Estimating key epidemiological parameters, such as incubation period, serial interval (SI), generation interval (GI) and latent period, is essential to quantify the transmissibility and effects of various interventions of COVID-19. These key parameters play a critical role in quantifying the basic reproduction number. With the hard work of epidemiological investigators in South Korea, estimating these key parameters has become possible based on infector-infectee surveillance data of COVID-19 between February 2020 and April 2021. Herein, the mean incubation period was estimated to be 4.9 days (95% CI: 4.2, 5.7) and the mean generation interval was estimated to be 4.3 days (95% CI: 4.2, 4.4). The mean serial interval was estimated to be 4.3, with a standard deviation of 4.2. It is also revealed that the proportion of presymptomatic transmission was ~57%, which indicates the potential risk of transmission before the disease onset. We compared the time-varying reproduction number based on GI and SI and found that the time-varying reproduction number based on GI may result in a larger estimation of Rt, which refers to the COVID-19 transmission potential around the rapid increase of cases. This highlights the importance of considering presymptomatic transmission and generation intervals when estimating the time-varying reproduction number.


Effect of thymosin β4 on lipopolysaccharide‑stimulated brain microvascular endothelial cell remodeling: A possible role in blood‑brain barrier injury.
War veterans, in particular, are more prone to mental illness as they are more likely to have encountered multiple traumatic brain injuries (TBIs) whilst serving on active duty in war zone areas. A TBI is known to cause mortality or serious neurological disabilities among survivors and elicits a number of pathological processes, including neuroinflammation and blood brain barrier (BBB) disruption, leading to secondary brain damage and subsequent impairment of the neurovascular unit. Although several drugs exhibit promising effects for TBI, the repertoire of currently available therapeutic strategies remains limited. Thymosin 4 (Tβ4) is a 43-amino acid G-acting sequestering peptide that confers neuroprotective potential in TBI models. However, its role in BBB function remains unclear. Further research into the mechanism of BBB disruption induced by TBI and its specific role in neurovascular pathophysiology is necessary. In the present study, the protective effects of Tβ4 in lipopolysaccharide (LPS)-stimulated gene expression of several tight junction proteins, inflammatory genes, apoptotic genes, and adhesion genes in human brain microvascular endothelial cells (hBMVECs), one of the pivotal cell types in the BBB, were reported. The results suggested that pretreatment with Tβ4 reversed the LPS-induced damage of BBB components in hBMVECs. Furthermore, these results identified neuregulin 1 as a possible target for Tβ4. Therefore, it is proposed that Tβ4-mediated cellular signaling in hBMVEC may be vital for understanding the association between the BBB and TBI pathophysiology, which warrants further investigation.


[Volume retention in heart failure, nephrotic syndrome, and liver cirrhosis].
Volume retention in heart failure, nephrotic syndrome, and liver cirrhosis reflects pathological changes in homeostatic mechanisms that regulate the extracellular volume (sympathetic activity, renin-angiotensin-aldosterone system [RAAS], natriuretic peptides) and plasma osmolality (antidiuretic hormone [ADH]). In heart failure and liver cirrhosis, these changes are induced by a reduction of the effective circulating volume, which is the part of the extracellular fluid that is within the arterial system and effectively perfusing the tissues. This reduction in the effective circulating volume is caused by reduced cardiac output (heart failure), or by splanchnic vasodilatation with arterial underfilling (liver cirrhosis). In both cases, baroreceptors in both the carotid sinuses and in the glomerular afferent arterioles upregulate RAAS- and sympathetic activity, resulting in systemic vasoconstriction and renal sodium (and volume) retention. More severe reductions in the effective circulating volume may additionally stimulate ADH release, thus increasing the reabsorption of free water with subsequent hyponatriemia. In nephrotic syndrome, volume retention results either directly from the primary renal disease, which induces renal sodium and volume retention ("overfilling"), or indirectly from the reduced plasma oncotic pressure due to hypoalbuminemia, which induces a fluid shift from the intravascular to the interstitial space ("underfilling") with subsequent acitivation of baroreceptors and secondary sodium and volume retention.


Development and Validation of a Rapid LC-MS/MS Method for Simultaneous Determination of Kaempferol and Quercetin in Thespesia populnea Extract.
In this study, a simple and rapid LC with tandem MS method was developed and validated for the simultaneous determination of kaempferol and quercetin in Thespesia populnea extract. The compounds were eluted using a Gemini C18 column (50 × 2.0 mm, 3 μm), with the mobile phase consisting of acetonitrile-0.3% formic acid in water at the flow rate of 0.400 mL/min. The assay exhibited a linear dynamic range of 25-2500 ng/mL for both kaempferol and quercetin. The values for intra- and interday precision and accuracy were well within the generally accepted criteria for analytical methods (<15%). Selectivity, linearity, LOD, LOQ, accuracy, and precision were evaluated for both analytes. The proposed method is accurate and sensitive and can be used for the routine quantification of kaempferol and quercetin in the herbal extract and in polyherbal formulations.


In vitro differentiation process of human Wharton's jelly mesenchymal stem cells to male germ cells in the presence of gonadal and non-gonadal conditioned media with retinoic acid.
Human umbilical Wharton's jelly-derived mesenchymal stem cells (HWJMSCs) are the best candidate to get plentiful stem cells and differentiate them to germ cells under appropriate conditions to treat infertility. We sought to determine under which conditions HWJMSCs could form male germ cells in vitro. So, HWJMSCs were differentiated to male germ cells under a mixture of bone morphogenetic protein-4 (BMP-4) and testicular and placental culture condition (TCC and PCC) medium followed by retinoic acid for 21 d. In the present study, the HWJMSCs were obtained from Wharton's jelly of umbilical cords of male neonates delivered by cesarean section. At the third passage, mesenchymal stem cell markers and differentiation to osteocytes and adipocytes were investigated. Then, HWJMSCs were induced to differentiate into male germ cells in the presence of BMP-4, all-trans retinoic acid, PCC, and TCC for 21 d. The profile of c-Kit, DDX4, Piwil2, and Dazl gene expression was evaluated by qPCR and ICC. Data was analyzed by ANOVA test. After 3 wk of treatment with different reagents, the morphology of these spindle-like cells changed to shiny clusters and germ cell-specific markers in mRNA were upregulated in both TCC + retinoic acid (RA) and BMP-4 + RA. Induction of HWJMSCs with TCC in the presence of RA resulted in significant upregulation (P ≤ 0.05) of all germ cell-specific genes (c-Kit 2.6795 ± 0.75, DDX4 4.3188 ± 1.18, Piwil2 4.9962 ± 1.55, Dazl 6.1199 ± 0.78) compared to control and PCC + RA. Our results indicated that TCC and RA are involved in human germ cell development. Moreover, BMP signaling also induced differentiation. Our findings provide a novel effective approach for generation of germ cells in vitro and studying the interaction of germ cells with their niche. Our work represents an essential step toward gaining knowledge of the molecular properties of HWJMSCs in the field of cell therapy. We demonstrated that under a suitable situation, HWJMSCs have the ability to differentiate into germ cells and this provides an excellent pattern to study infertility cause and cure.


Low energy hydrogenation products of extended pi systems CnH2x: a density functional theory search strategy, benchmarked against CCSD(T), and applied to C60.
An approach for the systematic determination of particularly stable hydride compositions C(n)H(2x) of a fullerene C(n) is presented. The study is divided into three parts. First, a CCSD(T) benchmark study on benzene and naphthalene hydrogenation is carried out. We show that the TPSS and BP86 functionals give more reliable relative isomer energies and reaction energies than B3LYP, when compared to CCSD(T) calculations. We therefore recommend BP86 for use on fullerenes. In the second part, a scheme for reduction in the immense number of possible fullerene hydride isomers is proposed. The scheme is based on thermodynamic sampling and involves density functional based tight binding as fast preselection method. The testing of the approach for C(60) constitutes the last part of the study. A low energy pathway for C(60)H(36) production is determined. Particularly stable structures are identified through analysis of the reaction energies along this pathway. These are C(60)H(2x) with 2x=18, 30, and 36. The good agreement of these results with the experimental and previous theoretical data suggests that our method is reliable and can be used to study fullerene hydrogenation.


More oxygen during development enhanced flight performance but not thermal tolerance of Drosophila melanogaster.
High temperatures can stress animals by raising the oxygen demand above the oxygen supply. Consequently, animals under hypoxia could be more sensitive to heating than those exposed to normoxia. Although support for this model has been limited to aquatic animals, oxygen supply might limit the heat tolerance of terrestrial animals during energetically demanding activities. We evaluated this model by studying the flight performance and heat tolerance of flies (Drosophila melanogaster) acclimated and tested at different concentrations of oxygen (12%, 21%, and 31%). We expected that flies raised at hypoxia would develop into adults that were more likely to fly under hypoxia than would flies raised at normoxia or hyperoxia. We also expected flies to benefit from greater oxygen supply during testing. These effects should have been most pronounced at high temperatures, which impair locomotor performance. Contrary to our expectations, we found little evidence that flies raised at hypoxia flew better when tested at hypoxia or tolerated extreme heat better than did flies raised at normoxia or hyperoxia. Instead, flies raised at higher oxygen levels performed better at all body temperatures and oxygen concentrations. Moreover, oxygen supply during testing had the greatest effect on flight performance at low temperature, rather than high temperature. Our results poorly support the hypothesis that oxygen supply limits performance at high temperatures, but do support the idea that hyperoxia during development improves performance of flies later in life.


Selective synthesis of functionalized, tertiary silanes by diastereoselective rearrangement-addition.
[reaction: see text] Treatment of hydroxy-substituted silyl epoxides with Grignard reagents induces a 1,2-carbon shift to reveal alpha-silyl aldehydes, which are trapped by highly diastereoselective addition reactions of the Grignard reagent. The starting epoxides are readily accessible from propargylic alcohols by regio- and diastereoselective hydrosilylation and epoxidation reactions. In addition to providing functionalized tertiary silane products, the method is shown to offer a tertiary olefin synthesis through chemo- and diastereoselective Peterson elimination of the product tertiary silane diols.


Experimental and theoretical investigations of H2O-Ar.
We have used continuous-wave cavity ring-down spectroscopy to record the spectrum of H2O-Ar in the 2OH excitation range of H2O. 24 sub-bands have been observed. Their rotational structure (Trot = 12 K) is analyzed and the lines are fitted separately for ortho and para species together with microwave and far infrared data from the literature, with a unitless standard deviation σ=0.98 and 1.31, respectively. Their vibrational analysis is supported by a theoretical input based on an intramolecular potential energy surface obtained through ab initio calculations and computation of the rotational energy of sub-states of the complex with the water monomer in excited vibrational states up to the first hexad. For the ground and (010) vibrational states, the theoretical results agree well with experimental energies and rotational constants in the literature. For the excited vibrational states of the first hexad, they guided the assignment of the observed sub-bands. The upper state vibrational predissociation lifetime is estimated to be 3 ns from observed spectral linewidths.


Prognostic value of total bilirubin in patients with acute myocardial infarction: A meta-analysis.
Experimental data obtained in animal models supported the protective role of bilirubin. However, clinical studies regarding the prognostic role of total bilirubin in patients with acute myocardial infarction (AMI) are conflicting. We, therefore, undertook this meta-analysis to evaluate the prognostic value of serum total bilirubin in AMI patients. Relevant studies were searched from PubMed and EMBASE databases up to April 15, 2018. Studies evaluating the outcomes in relation to serum total bilirubin in AMI patients and reporting multivariable-adjusted risk estimate of the prognostic value were eligible. The outcome measures were major adverse cardiac events (MACEs), cardiovascular death, and all-cause mortality. Six studies involving 14,554 AMI patients were identified. Meta-analysis indicated that higher total bilirubin was associated with an increased risk of MACEs (risk ratio [RR] 1.65; 95% confidence intervals [CI] 1.25-2.19) and cardiovascular death (RR 2.12; 95%CI 1.24-3.64). However, higher serum total bilirubin did not significantly increase all-cause mortality risk (RR 1.31; 95%CI 0.75-2.28). Subgroup analyses by the types of AMI and study design supported the pooled results. Higher serum total bilirubin level is a predictor of MACEs and cardiovascular death in patients with AMI. However, interpretation of these findings should be with caution due to the impact of cardiac dysfunction after AMI.


Physiologic factors contributing to a transition in oral immunity among mechanically ventilated adults.
Ventilator-associated pneumonia (VAP), a specific type of nosocomial pneumonia, occurs in approximately 21% of patients in intensive care, and the mortality can be as high as 71%. VAP causes considerable mortality and morbidity, and it exponentially increases health care costs. The incidence of VAP is associated with oropharyngeal colonization of gram-negative bacteria. Within 48 h of hospital admission, the composition of the oropharyngeal flora of critically ill patients undergoes a change from the usual gram-positive streptococci and dental pathogens to a predominant gram-negative flora that includes more virulent organisms, which predispose patients to VAP. Identification and understanding of this oral transition from gram-positive to predominantly gram-negative flora may assist health care professionals in differentiating among oral immune markers that suggest compromised immunity. The purpose of this article is to provide a review of the literature that promotes an understanding of current knowledge about the transition of oral immunity in mechanically ventilated patients.


Electronic reanimation of facial paralysis--a feasibility study.
We set out to adapt the concept of functional electrical stimulation to the reanimation of the paralyzed face. In the New Zealand white rabbit model we studied the strength-duration curves of both innervated and denervated facial muscles. We next studied the electromyographic signals corresponding to different strengths of contraction of innervated facial muscles. With Teflon-coated stainless steel electrodes implanted at opposite ends of the denervated muscle groups under study, bipolar stimulation yielded useful mimetic function that was modifiable by varying the voltage output and the rate of pulse generation. We demonstrated that an electronic circuit can indeed respond to the voltage generated within a functioning facial muscle, and then reproducibly trigger a corresponding graphic signal in synchrony with the mimetic function. The next step will be to adapt an electronic circuit that will deliver a predetermined electrical current to a denervated facial muscle in response to a determined generated voltage in the contralateral corresponding innervated facial muscle.


Associations of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Polymorphism With Cognitive Impairment Among the Oldest-Old in China.
Recent literature suggested that ALDH2 mutation is associated with alcohol metabolism, and ethanol intake might jointly increase the risk of Alzheimer's disease (AD) in mice. However, it is unclear whether this synergistic effect exists among humans. We examined the associations of four single nucleotide polymorphisms (SNPs) on aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) genes (i.e., ALDH2 rs671, ADH1B rs1229984, ADH1B rs1042026, and ADH1C rs1693482) and cognitive impairment among the oldest-old. We also investigated whether this association was modified by ethanol intake from alcohol consumption. Data were from the Chinese Longitudinal Healthy Longevity Survey genetic sub-study, including 1,949 participants aged over 90 years. Participants with a Mini-Mental State Examination (MMSE) score of < 18 were considered cognitively impaired. Alcohol consumption was categorized as heavy, moderate, or never drinkers. With the dominant model, carrying A allele on rs671, C allele on rs1229984, and T allele on rs1042026 was associated with 33% (95% confidence interval [CI]: 5%, 69%), 33% (95% CI: 2%, 75%), and 29% (95% CI: 3%, 62%) higher odds of cognitive impairment in the multivariable-adjusted logistic model, respectively. We did not observe a significant interaction between those SNPs and alcohol consumption. Among the oldest-old, carrying ALDH2 rs671 mutation was associated with higher odds of cognitive impairment independent of alcohol consumption.


Diagnosis of toxoplasmosis by joint detection of immunoglobulin A and immunoglobulin M.
An indirect immunofluorescence test with total anti-human immunoglobulin conjugate (IgG,A,M-IIF) can be used for joint detection of immunoglobulin A (IgA) and IgM antibodies, provided serum IgG is previously absorbed with anti-human IgG. To determine the validity of the IgG,A,M-IIF assay with absorbed sera, the results obtained were compared with those obtained by methods routinely used for the detection of acute-phase markers, IgA and IgM IIF and enzyme immunoassay. Accordingly, 114 serum samples were selected from patients showing titers of > or = 1:1,024 by IgG,A,M-IIF. (i) In 90 of the samples, neither IgA nor IgM was detected by any of the methods employed; (ii) the remaining 24 samples showed IgA and/or IgM. In all cases, the IgG,A,M-IIF assay with absorbed sera was positive. These comparative data support the use of IgG,A,M-IIF, performed with absorbed and unabsorbed sera simultaneously, for determining the presence of specific IgG, IgA, and IgM by employing a single technique (IIF), one conjugate (anti-IgG,A,M), and only one sample (with and without previous absorption), thus providing a useful initial tool for the diagnosis of toxoplasmosis.


Marek's Disease Virus Infection Induced Mitochondria Changes in Chickens.
Mitochondria are crucial cellular organelles in eukaryotes and participate in many cell processes including immune response, growth development, and tumorigenesis. Marek's disease (MD), caused by an avian alpha-herpesvirus Marek's disease virus (MDV), is characterized with lymphomas and immunosuppression. In this research, we hypothesize that mitochondria may play roles in response to MDV infection. To test it, mitochondrial DNA (mtDNA) abundance and gene expression in immune organs were examined in two well-defined and highly inbred lines of chickens, the MD-susceptible line 72 and the MD-resistant line 63. We found that mitochondrial DNA contents decreased significantly at the transformation phase in spleen of the MD-susceptible line 72 birds in contrast to the MD-resistant line 63. The mtDNA-genes and the nucleus-genes relevant to mtDNA maintenance and transcription, however, were significantly up-regulated. Interestingly, we found that POLG2 might play a potential role that led to the imbalance of mtDNA copy number and gene expression alteration. MDV infection induced imbalance of mitochondrial contents and gene expression, demonstrating the indispensability of mitochondria in virus-induced cell transformation and subsequent lymphoma formation, such as MD development in chicken. This is the first report on relationship between virus infection and mitochondria in chicken, which provides important insights into the understanding on pathogenesis and tumorigenesis due to viral infection.


Multi-scale mechanobiological model for skeletal muscle hypertrophy.
Skeletal muscle adaptation is correlated to training exercise by triggering different signaling pathways that target many functions; in particular, the IGF1-AKT pathway controls protein synthesis and degradation. These two functions regulate the adaptation in size and strength of muscles. Computational models for muscle adaptation have focused on: the biochemical description of signaling pathways or the mechanical description of muscle function at organ scale; however, an interrelation between these two models should be considered to understand how an adaptation in muscle size affects the protein synthesis rate. In this research, a dynamical model for the IGF1-AKT signaling pathway is linked to a continuum-mechanical model describing the active and passive mechanical response of a muscle; this model is used to study the impact of the adaptive muscle geometry on the protein synthesis at the fiber scale. This new computational model links the signaling pathway to the mechanical response by introducing a growth tensor, and links the mechanical response to the signaling pathway through the evolution of the protein synthesis rate. The predicted increase in cross sectional area (CSA) due to an 8 weeks training protocol excellently agreed with experimental data. Further, our results show that muscle growth rate decreases, if the correlation between protein synthesis and CSA is negative. The outcome of this study suggests that multi-scale models coupling continuum mechanical properties and molecular functions may improve muscular therapies and training protocols.


Active control on topological interface states of elastic wave metamaterials with double coupled chains.
Topological elastic wave metamaterials have shown significant advantages in manipulating wave propagation and realizing localized modes. However, topological properties of most mechanical metamaterials are difficult to change because of structural limitations. This work proposes the elastic wave metamaterials with double coupled chains and active control, in which band inversion and topological interface modes can be achieved by flexibly tuning negative capacitance circuits. Finite element simulations and experiments are performed to demonstrate the topological interface modes, which show good agreements with the theoretical results. This research seeks to provide effective strategies for the design and application of topological elastic wave metamaterials.


Joint Raman spectroscopic and quantum chemical analysis of the vibrational features of Cs2RuO4.
The Raman spectroscopic characterization of the orthorhombic phase of Cs2RuO4 was carried out by means of group theory and quantum chemical analysis. Multiple models based on ruthenate (VI+) tetrahedra were tested, and characterization of all the active Raman modes was achieved. A comparison of Raman spectra of Cs2RuO4, Cs2MoO4, and Cs2WO4 was also performed. Raman laser heating induced a phase transition from an ordered to a disordered structure. The temperature-phase transition was calculated from the anti-Stokes/Stokes ratio and compared with the ones measured at macroscopic scale. The phase transition is connected with tilting and/or rotations of RuO4 tetrahedra, which lead to a disorder at the RuO4 sites. © 2015 The Authors. Journal of Raman Spectroscopy published by John Wiley & Sons Ltd.


Plasminogen activator activity in cultures from human tissues. An immunological and histochemical study.
Human tissues and cells from pre- and postnatal life were cultivated and studied for plasminogen activator activity. Cultures were obtained from kidney, renal blood vessels, ureter, bladder, lung, and heart. Local activator activity of cells was demonstrated by histochemical techniques. Activator released by cells into the supernatant culture media was assayed by fibrin plate techniques and was investigated for immunological identity using specific antisera to an activator of human origin, urokinase (UK). Plasminogen activator was produced in primary cultures where cells retain specific functions and generally reflect the enzyme pattern of the tissues of origin. Cells from fetal and adult sources were found to yield activator antigenically identical to UK, as well as activator activity which differed from that of UK in immunoassays and which may represent tissue type activator. Such activity was released after injury or death of cells while UK was produced in cultures containing live, metabolizing cells. Primary cultures of kidney confirmed that this organ is a rich source of UK and demonstrated, in addition, that UK is produced from the early stages of gestation and in increasing amounts thereafter. However, primary cultures also demonstrated that the ability to produce UK is not limited to the kidney but is a function of cells which are distributed widely in body tissues. Thus, activator antigenically identical to UK accumulated progressively after many refeedings in culture supernates of fetal lung and ureter, as well as in supernates of renal blood vessels of adults. These findings indicate continuous formation of UK by the cultured cells and, furthermore, provide evidence of UK production in blood vessels. In cultures from other tissues, particularly those from fetal heart and adult lung and bladder, investigation of activator was hindered by inhibitory activity which accumulated in the supernates. Such activity was derived from cells in culture and was directed selectively against UK, indicating that inhibitor as well as UK are produced by cells of various organs of the body. Plasminogen activator also was produced by serially propagated cells, diploid and heteroploid. However, only diploid cell lines retained activator activity of the original tissues and continued to produce activator antigenically identical to UK. In contrast, heteroploid line appeared to have lost the ability to form UK by yielded activator activity that differed from that of UK in immunoassays. Serially propagated cells thus provide an additional tool for in vitro study of plasminogen activator and may facilitate investigation of the fibrinolytic system in man.


Global seasonality of rotavirus infections.
Data from 34 studies of the etiology of childhood diarrhoea were compiled in order to investigate the seasonal patterns of rotavirus gastroenteritis and consider their implications for transmission of the virus. Rotavirus was detected in 11-71% of children with diarrhoea, and the median rate of detection (33%) was independent of the level of economic development or geographical region of the study area, as well as of the method of detection used. While rotavirus infections have been called a winter disease in the temperate zones, we found that their incidence peaked in winter primarily in the Americas and that peaks in the autumn or spring are common in other parts of the world. In the tropics, the seasonality of such infections is less distinct and within 10 degrees latitude (north or south) of the equator, eight of the ten locations exhibited no seasonal trend. Throughout most of the world, rotavirus is present all the year round, which suggests that low-level transmission could maintain the chain of infection. The virus is spread by the faecal-oral route but airborne or droplet transmission has also been postulated. The epidemiology of rotavirus--its seasonality in the cooler months, its universal spread in temperate and tropical zones in developed and less developed settings--more closely resembles that of childhood viruses that are spread by the respiratory route (such as measles) than that of common enteric pathogens that are spread predominantly by the faecal-oral route.


The Ultrafast Energy Transfer Process in Purple Bacteria Photosynthetic Reaction Center.
The ultrafast energy transfer process, which takes place in femtosecond time range, in bacterial photosynthetic reaction center RS601 was investigated using femtosecond pump-probe technique with selective excitation. Upon 755 nmexcitation, the excited state of bacteriopheophytin H decayed to bacteriochlorophyll B with a time constant of about 130 fs, while the excited state of B transported the energy to its energy acceptor, the dimeric bacteriochlorophyll P, in about 240 fs with the 800 nm excitation. The internal conversion process between the upper and lower exciton levels of special pair P might exist upon the excitation of 850 nm pulses. In addition, from the results obtained in our experiments, the charge separation and electron transfer from P to the acceptor H was also observed via the real intermediate B within a few picoseconds.


The historical backgrounds of the ministry of health foundation in Iran.
The early efforts for promotion of public health measures and prevention of fatal epidemic diseases in Iran date back to the second half of the 19th century. Based on historical records, the informal protosanitary councils had existed since the early 1850s, but a new formal health institution called "Sanitary Council", or "Majles-e Hefz al-Sehheh" was founded in 1881. Then, it was reestablished as a permanent council in 1904. The Sanitary Council was the only major public health authority under the auspices of "Ministry of the Interior" up to 1920. Then the Ministry of Health and Charity Affairs or "Vezarat-e Sehhyeh va Omuor-e Kheiryyeh" was founded in 1920, but it was dissolved in 1921. Between 1921 and 1941, there was no ministry of public health in Iran and during this period, the public health and medical affairs were mananged by the Public Health Administration known as Sehhyeh Koll-e Mamlekati that was established in 1926 and finally in 1941, the Ministry of Health ( Vezarat-e Behdari) was founded. Presented here, is the historical backgrounds of the foundation of the Ministry of Health in Iran, as well as the list of the Health Ministers between 1941 and 1979.


T cell activator-carrying extracellular vesicles induce antigen-specific regulatory T cells.
The mechanism of antigen-specific regulatory T cell (Treg ) induction is not yet fully understood. Curcumin has an immune regulatory function. This study aims to induce antigen-specific Tregs by employing extracellular vesicles (EVs) that carry two types of T cell activators. Two types of T cell activators, ovalbumin (OVA)/major histocompatibility complex-II (MHC-II) and tetramethylcurcumin (FLLL31) (a curcumin analog) were carried by dendritic cell-derived extracellular vesicles, designated OFexo. A murine model of allergic rhinitis (AR) was developed with OVA as the specific antigen. AR mice were treated with a nasal instillation containing OFexo. We observed that OFexo recognized antigen-specific T cell receptors (TCR) on CD4+ T cells and enhanced Il10 gene transcription in CD4+ T cells. Administration of the OFexo-containing nasal instillation induced antigen-specific type 1 Tregs (Tr1 cells) in the mouse airway tissues. OFexo-induced Tr1 cells showed immune suppressive functions on CD4+ T cell proliferation. Administration of OFexo efficiently alleviated experimental AR in mice. In conclusion, OFexo can induce antigen-specific Tr1 cells that can efficiently alleviate experimental AR. The results suggest that OFexo has the translational potential to be employed for the treatment of AR or other allergic disorders.


Skeleton Filter: A Self-Symmetric Filter for Skeletonization in Noisy Text Images.
Robustly computing the skeletons of objects in natural images is difficult due to the large variations in shape boundaries and the large amount of noise in the images. Inspired by recent findings in neuroscience, we propose the Skeleton Filter, which is a novel model for skeleton extraction from natural images. The Skeleton Filter consists of a pair of oppositely oriented Gabor-like filters; by applying the Skeleton Filter in various orientations to an image at multiple resolutions and fusing the results, our system can robustly extract the skeleton even under highly noisy conditions. We evaluate the performance of our approach using challenging noisy text datasets and demonstrate that our pipeline realizes state-of-the-art performance for extracting the text skeleton. Moreover, the presence of Gabor filters in the human visual system and the simple architecture of the Skeleton Filter can help explain the strong capabilities of humans in perceiving skeletons of objects, even under dramatically noisy conditions.


Dupilumab for the treatment of atopic dermatitis: A clinical trial review.
Current treatment options for moderate-to-severe atopic dermatitis (AD) are limited and have potentially dangerous side effects. Dupilumab is a novel monoclonal antibody that was recently studied in adult patients with moderate-to-severe AD. Dupilumab inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in asthma. Considering that both AD and asthma are Th2 cell-mediated inflammatory processes, it is reasonable to suspect that dupilumab would be beneficial in AD.` This article is a review of the one major clinical trial that assessed the efficacy of dupilumab in patients with AD. Its goal is to provide a comparison to the current modalities for the treatment of AD and expert insight regarding future studies. The results of this study are a significant therapeutic advancement. Dupilumab was shown to provide a mean percent change in Eczema Area and Severity Index score of -74% ± 3.6, in addition to, statistically and clinically significant reductions the severity, symptomatology, and morbidity associated with AD. However, the small sample size makes it difficult to assess the magnitude of this effect. As a result, dupilumab will likely be reserved for cases of severe AD unresponsive to traditional modalities.


Effect of metoprolol on chest pain in acute myocardial infarction.
A total of 1395 patients aged 40 to 74 years were included in a double blind trial with the beta 1 selective blocker metoprolol in suspected acute myocardial infarction. Metoprolol was given intravenously (15 mg) as soon as possible after admission to hospital followed by 200 mg daily for three months. A placebo was given in the same manner. The severity of chest pain in the acute phase was calculated by recording the number of injections of analgesics given and the time from the start of blind treatment to the time when the last analgesic was given (duration of pain). The patients receiving metoprolol were given a lower mean number of injections of analgesics during the first four days and after randomisation than those receiving a placebo. The estimated duration of pain was shorter in the metoprolol group than in the placebo group. These effects were related to the initial heart rate, the initial systolic blood pressure, and the final site of the infarct as determined electrocardiographically. Thus metoprolol given in the acute phase of suspected or definite myocardial infarction appears to reduce the severity of chest pain.


Identification of cis-acting promoter elements important for expression of the mouse glycoprotein hormone alpha-subunit gene in thyrotropes.
The glycoprotein hormone alpha-subunit gene is expressed in a cell-specific manner in the anterior pituitary and placenta. Previous studies have shown that the region between -178 to -111 is indispensable for placental-specific expression of the human alpha-subunit gene. Using gene transfer techniques with chimeric luciferase plasmids, this report identifies regions of the mouse alpha-subunit promoter that are important for transcriptional activation in primary thyrotropic cells. Transient expression of a series of 5' flanking DNA deletions resulted in stepwise reductions of basal promoter activity between -480 to -417 (4-fold), -254 to -177 (5-fold), and -177 to -120 (3.5-fold). DNase-I protection analysis with nuclear extracts from thyrotropic tumor cells revealed specific protein-DNA interactions within each of these functionally defined regions. These were mapped to positions -474 to -452, -447 to -419, -213 to -170, and -158 to -101 within the 5' flanking region. In contrast, in mouse fibroblast L-cells no significant difference in alpha-subunit promoter activity was found by deleting the region from -480 to -177. However, a 3-fold decrease, similar to that found in primary thyrotropes, was found by deleting the region from -177 to -120. Further, a smaller region between -138 and -122 was the only area detected by the DNase-I protection assay using L-cell nuclear extracts. Thus, several cis-acting promoter elements located up-stream of position -177 are important for expression in thyrotropes. These elements also bind nuclear factors present in thyrotropes but not in nonpituitary fibroblasts and, therefore, differ from those mediating expression of the human alpha-subunit gene in the placenta.


Analyzing Signal Peptides for Secretory Production of Recombinant Diagnostic Antigen B8/1 from Echinococcus granulosus: An In silico Approach.
Recombinant AgB8/1 as the most evaluated antigen for serological diagnosis of Cystic Echinococcosis (CE) can provide early and accurate diagnosis for proper management and treatment of the disease. Thus, the secretory production of this recombinant protein is the main goal and the application of signal peptides at the N terminus of the desired protein can help to achieve this goal. The present study applied few bioinformatics tools to evaluate several signal peptides to offer the best candidate for extracellular production of AgB8/1 of Echinococcus granulosus in Escherichia coli. The sequences related to signal peptides were obtained from "Signal Peptide Website" and were checked by "UniProt". In addition, UniProt was employed to retrieve the sequence of AgB8/1. Then, the probable signal peptide sequences and their cleavage site locations were determined by SignalP 4.1 followed by evaluation of their physicochemical features, using ProtParam. The solubility of the target recombinant proteins was accessed by SOLpro. Finally, PRED-TAT and ProtCompB were implemented to predict protein secretion pathways and final destinations. Among the 39 candidate signal peptides, ENTC2_STAAU and ENTC1_STAAU are the best ones which are stable and soluble in connection with AgB8/1 and can secrete target protein through Sec pathway. The signal peptides recommended in this investigation are valuable for rational designing of secretory stable and soluble AgB8/1. Such information is useful for future experimental production of the mentioned antigen.


Bayesian approach for assessing non-inferiority in a three-arm trial with pre-specified margin.
Non-inferiority trials are becoming increasingly popular for comparative effectiveness research. However, inclusion of the placebo arm, whenever possible, gives rise to a three-arm trial which has lesser burdensome assumptions than a standard two-arm non-inferiority trial. Most of the past developments in a three-arm trial consider defining a pre-specified fraction of unknown effect size of reference drug, that is, without directly specifying a fixed non-inferiority margin. However, in some recent developments, a more direct approach is being considered with pre-specified fixed margin albeit in the frequentist setup. Bayesian paradigm provides a natural path to integrate historical and current trials' information via sequential learning. In this paper, we propose a Bayesian approach for simultaneous testing of non-inferiority and assay sensitivity in a three-arm trial with normal responses. For the experimental arm, in absence of historical information, non-informative priors are assumed under two situations, namely when (i) variance is known and (ii) variance is unknown. A Bayesian decision criteria is derived and compared with the frequentist method using simulation studies. Finally, several published clinical trial examples are reanalyzed to demonstrate the benefit of the proposed procedure.


Adaptation of a ladder beam walking task to assess locomotor recovery in mice following spinal cord injury.
Locomotor impairments after spinal cord injury (SCI) are often assessed using open-field rating scales. These tasks have the advantage of spanning the range from complete paralysis to normal walking; however, they lack sensitivity at specific levels of recovery. Additionally, most supplemental assessments were developed in rats, not mice. For example, the horizontal ladder beam has been used to measure recovery in the rat after SCI. This parametric task results in a videotaped archival record of the event, is easily administered, and is unambiguously scored. Although a ladder beam apparatus for mice is available, its use in the assessment of recovery in SCI mice is rare, possibly because normative data for uninjured mice and the type of step misplacements injured mice exhibit is lacking. We report the development of a modified ladder beam instrument and scoring system to measure hindlimb recovery in vertebral T9 contusion spinal cord injured mice. The mouse ladder beam allows for the use of standard parametric statistical tests to assess locomotor recovery. Ladder beam performance is consistent across four strains of mice, there are no sex differences, and inter-rater reliability between observers is high. The ladder beam score is proportional to injury severity and can be used to easily separate mice capable of weight-supported stance up to mice with consistent forelimb to hindlimb coordination. Critically, horizontal ladder beam testing discriminates between mice that score identically in terms of stepping frequency in open-field testing.


Quantifying the effect of investors' attention on stock market.
The investors' attention has been extensively used to predict the stock market. Different from existing proxies of the investors' attention, such as the Google trends, Baidu index (BI), we argue the collective attention from the stock trading platforms could reflect the investors' attention more closely. By calculated the increments of the attention volume for each stock (IAVS) from the stock trading platforms, we investigate the effect of investors' attention measured by the IAVS on the movement of the stock market. The experimental results for Chinese Securities Index 100 (CSI100) show that the BI is significantly correlated with the returns of CSI100 at 1% significance level only in 2014. However, it should be emphasized that the correlation of the new proposed measure, namely IAVS, is significantly at 1% significance level in 2014 and 2015. It shows that the effect of the measure IAVS on the movement of the stock market is more stable and significant than BI. This study yields important invest implications and better understanding of collective investors' attention.


Immunoperoxidase labelling of rat brain sections with sera from patients with paraneoplastic cerebellar degeneration and systemic neoplasia.
Sera from patients with systemic cancer found by immunofluorescence staining to have antibodies to human cerebellar cell populations were reacted with vibratome sections of rat cerebellum and examined by peroxidase-antiperoxidase (PAP) methods. Seven patients with clinically or pathologically confirmed paraneoplastic cerebellar degeneration and two neurologically normal patients with high titers of anticerebellar antibodies were studied. Sera from all antibody-positive patients, but not from controls, produced intense staining of brain sections. Sera from patients with ovarian adenocarcinoma reacted predominantly with Purkinje cells and neurons within brainstem nuclei. Sera from patients with oat cell carcinoma and one patient with ductal carcinoma of the breast produced nuclear and cytoplasmic staining of neurons throughout the central nervous system. Serum from a patient with Hodgkin's disease labeled the peripheries of Purkinje cells and Golgi II cells. Serum from a patient with mixed mesodermal sarcoma of the ovary labeled Purkinje cells, basket cells, and scattered astrocytes. Staining of extraneural tissues was not observed. This study confirms the presence of antineural antibodies in patients with systemic neoplasia with and without paraneoplastic cerebellar degeneration and suggests that the antigens recognized by this antibody response may vary with the associated neoplasm.


Reconnecting in the Face of Exclusion: Individuals with High Social Anxiety May Feel the Push of Social Pain, but not the Pull of Social Rewards.
Previous research has shown that high levels of trait social anxiety (SA) disrupt the social repair processes following a painful social exclusion, but the cognitive mechanisms involved in these processes and how trait SA may disrupt them remain unknown. We conducted a preregistered study on Prolific participants (N = 452) who were assigned to experience either social exclusion or inclusion and were then exposed to follow-up opportunities for social reconnection. Moderated mediation analyses revealed that irrespective of levels of SA, participants responded to social pain with heightened approach motivation and greater downstream positive affect. Exploratory analyses revealed that heightened desire to affiliate was driven by increased curiosity and attention to social rewards. Moreover, higher SA was associated with lower overall desire to affiliate and this relationship between SA and affiliation was mediated by diminished reward responsiveness. Findings highlight the roles of goal pursuit and social reward responsiveness in social repair and how high levels of trait SA may disrupt these processes. The online version contains supplementary material available at 10.1007/s10608-021-10263-z.


Changes in synaptic transmission properties due to the expression of N-type calcium channels at the calyx of Held synapse of mice lacking P/Q-type calcium channels.
P/Q-type and N-type calcium channels mediate transmitter release at rapidly transmitting central synapses, but the reasons for the specific expression of one or the other in each particular synapse are not known. Using whole-cell patch clamping from in vitro slices of the auditory brainstem we have examined presynaptic calcium currents (I(pCa)) and glutamatergic excitatory postsynaptic currents (EPSCs) at the calyx of Held synapse from transgenic mice in which the alpha(1A) pore-forming subunit of the P/Q-type Ca(2+) channels is ablated (KO). The power relationship between Ca(2+) influx and quantal output was studied by varying the number of Ca(2+) channels engaged in triggering release. Our results have shown that more overlapping Ca(2+) channel domains are required to trigger exocytosis when N-type replace P/Q-type calcium channels suggesting that P/Q type Ca(2+) channels are more tightly coupled to synaptic vesicles than N-type channels, a hypothesis that is verified by the decrease in EPSC amplitudes in KO synapses when the slow Ca(2+) buffer EGTA-AM was introduced into presynaptic calyces. Significant alterations in short-term synaptic plasticity were observed. Repetitive stimulation at high frequency generates short-term depression (STD) of EPSCs, which is not caused by presynaptic Ca(2+) current inactivation neither in WT or KO synapses. Recovery after STD is much slower in the KO than in the WT mice. Synapses from KO mice exhibit reduced or no EPSC paired-pulse facilitation and absence of facilitation in their presynaptic N-type Ca(2+) currents. Simultaneous pre- and postsynaptic double patch recordings indicate that presynaptic Ca(2+) current facilitation is the main determinant of facilitation of transmitter release. Finally, KO synapses reveal a stronger modulation of transmitter release by presynaptic GTP-binding protein-coupled receptors (gamma-aminobutyric acid type B receptors, GABA(B), and adenosine). In contrast, metabotropic glutamate receptors (mGluRs) are not functional at the synapses of these mice. These experiments reinforce the idea that presynaptic Ca(2+) channels expression may be tuned for speed and modulatory control through differential subtype expression.


Knee laxity does not vary with the menstrual cycle, before or after exercise.
An intriguing explanation for the disproportionately high rate of anterior cruciate ligament injury in female athletes is that the structural properties of the anterior cruciate ligament are affected by the menstrual hormones. Whether this actually occurs, however, is the subject of ongoing debate. (1) Anterior cruciate ligament laxity is different in the follicular, ovulatory, and luteal phases of the menstrual cycle, and (2) exercise exacerbates the difference in anterior cruciate ligament laxity in the 3 phases. Over the course of 10 weeks, repeated knee laxity measurements were taken on 27 high-level female athletes, before and after exercise. Point in the menstrual cycle was determined with charts of waking temperature and menstruation. The independent effects of menstrual phase and exercise were evaluated using generalized estimating equations. Data from 18 participants were included in the final analysis. There were no significant differences in anterior cruciate ligament laxity in any of the 3 menstrual phases, before or after exercise. Anterior cruciate ligament laxity is not significantly different during the follicular, ovulatory, and luteal phases of the menstrual cycle, and bicycling exercise does not exacerbate or create any differences in anterior cruciate ligament laxity.


A convolutional learning system for object classification in 3-D Lidar data.
In this brief, a convolutional learning system for classification of segmented objects represented in 3-D as point clouds of laser reflections is proposed. Several novelties are discussed: (1) extension of the existing convolutional neural network (CNN) framework to direct processing of 3-D data in a multiview setting which may be helpful for rotation-invariant consideration, (2) improvement of CNN training effectiveness by employing a stochastic meta-descent (SMD) method, and (3) combination of unsupervised and supervised training for enhanced performance of CNN. CNN performance is illustrated on a two-class data set of objects in a segmented outdoor environment.


Perils and positives of science journalism in Australia.
Scientists, science communicators and science journalists interact to deliver science news to the public. Yet the value of interactions between the groups in delivering high-quality science stories is poorly understood within Australia. A recent study in New Zealand on the perspectives of the three groups on the challenges facing science journalism is replicated here in the context of New South Wales and the Australian Capital Territory. While all three groups perceived the quality of science journalism as generally high, the limitations of non-specialists and public relation materials were causes for concern. The results indicate that science communicators are considered to play a valuable role as facilitators of information flow to journalists and support for scientists. Future studies on the influence and implications of interactions between these three groups are required.


[Effect of worksite dental health program on periodontal status--evaluation by CPITN and bleeding on probing at each tooth].
A dental health promotion program which aimed to prevent periodontal disease was carried out at a shipyard in Nagasaki Prefecture. Repeated tooth cleaning instruction and prophylaxis were conducted in order to adopt proper oral hygiene habits. The first 3 months of this program included 'Initial instruction,' and 'Regular instruction' were given every 6 months in following 2 years. The oral examination was carried out before and after Initial instruction, and at each Regular instruction. The effect of this program was evaluated by 2 measures: CPITN and Bleeding on probing. After this program, the rate of teeth with pockets 4 -5 mm deep or deeper (CPITN 3, 4) was decreased. In contrast, the rate of teeth with no sign of periodontal disease (CPITN 0) was increased remarkably: the percentage increased from 8% preinitial instruction to 40% with regular instruction. Both the rate and grade of teeth with bleeding on probing were decreased. These results indicated that this program was helpful in improving the periodontal status. CPITN and Bleeding on probing at each tooth as an evaluation measure made our analysis more detailed.


Antifungal compounds produced by Colletotrichum gloeosporioides, an endophytic fungus from Michelia champaca.
In this study, eight endophytic fungi were isolated from the leaves, stems and roots of Michelia champaca. The isolates were screened and evaluated for their antifungal, anticancer and acetylcholinesterase (AChE) inhibitory activities. All of the extracts exhibited potent activity against two evaluated phytopathogenic fungi. Chemical investigation of EtOAc extracts of the endophytic fungus Colletotrichum gloeosporioides resulted in the isolation of one new compound, 2-phenylethyl 1H-indol-3-yl-acetate (1), and seven known compounds: uracil (2), cyclo-(S*-Pro-S*-Tyr) (3), cyclo-(S*-Pro-S*-Val) (4), 2(2-aminophenyl)acetic acid (5), 2(4-hydroxyphenyl)acetic acid (6), 4-hydroxy- benzamide (7) and 2(2-hydroxyphenyl)acetic acid (8). All of the compound structures were elucidated using 1D and 2D NMR and MS analyses. The antifungal and AChE inhibitory activities of compounds 1-8 were evaluated in vitro. Compound 1 exhibited promising activity against Cladosporium cladosporioides and C. sphaerospermum that was comparable to that of the positive control nystatin.


Placebo-controlled study of the effects of atomoxetine on bladder control in children with nocturnal enuresis.
Nocturnal enuresis is a condition in which children at least 5 years of age are incontinent of urine at night. Atomoxetine, a potent inhibitor of the presynaptic norepinephrine transporter, is used to treat attention-deficit/hyperactivity disorder (ADHD). This study tested the hypothesis that atomoxetine will provide significant therapeutic benefit for nocturnal enuresis in patients with the diagnosis of nocturnal enuresis. Atomoxetine's efficacy for improving nocturnal enuresis was studied in 87 pediatric subjects using an outpatient, multicenter, randomized, double-blind, parallel, placebo-controlled study. Efficacy was determined by measuring the mean number of dry nights per week using an intent-to-treat analysis of the primary outcome measure, the Dry Night Log-Parent Report (DNL-PR), a daily parent diary. Baseline and end point DNL-PR data were available from 42 atomoxetine-treated and 41 placebo-treated subjects. Atomoxetine increased the average number of dry nights per week by 1.47 compared with .60 for placebo (F = 7.06; df = (1, 75); p = 0.01). Fifteen atomoxetine-treated subjects (35.7%) had an increase of at least 2 dry nights per week compared with only 6 (14.6%) placebo-treated subjects (Fisher's exact test; p = 0.042). There were no significant differences in adverse events between the groups. Compared with placebo, atomoxetine treatment was associated with a significant increase in dry nights in children with nocturnal enuresis.


Polymorphism of the genus Isophya (Orthoptera, Phaneropteridae, Barbitistinae) revealed by RAPD.
The random amplified polymorphic DNA (RAPD-PCR) method was used to study the genetic polymorphism of 20 species of the genus Isophya. Each primer amplified a different set of DNA fragments, all oligonucleotides failed to generate any specific diagnostic band that could lead to the identification of Isophya species, and none of the amplified fragments were present in all species. RAPD markers detected a high level of polymorphism in all species. The data were in most cases not congruent with morphological subdivision to the species group and cytotaxonomic studies. The genetic lineages of Isophya seem to be in discordance with relationships proposed by systematists.


[3-dimensional cephalometry in orthodontics. The current possibilities of Cepha 3DT software].
A 3D cephalometric analysis method from a scanner acquisition, has been developed thanks to a long collaboration between the CIRAD modeling Laboratory and Jacques Treil. The model of skeletal description is based on eight landmarks related to the neuromatrical axis of facial growth (heads of the mallei, supraorbital, suborbital, submental points); it has been abundantly described. The purpose of this work consists in presenting the dentoalveolar level of the analysis. The description and the marking of the arches and the teeth mainly rest on the systematic use of a mathematical tool, the calculation of the central matrix of inertia, and on three fundamental choices: the identification of the dental arches from their constituting teeth leaving aside any alveolar marking, the marking of each tooth relative to the arch, as it can be observed by the orthodontist's eye, and not relative to the craniofacial architecture, the definition of the position of each tooth by the orientation of its coronoradicular axis and not its sole buccal side, Their uses in orthodontics are numerous: diagnosis, choice of the mechanics, therapeutic simulation, therapeutic follow up, analysis of the findings... Clinical applications illustrate the theoretical presentation.


Prioritizing molecular formulae identified by non-target analysis through high-throughput modelling: application to identify compounds with high human accumulation potential from house dust.
Because it is typically not possible to pursue compound identification efforts for all chemical features detected during non-target analysis (NTA), the need for prioritization arises. Here we propose a strategy that ranks chemical features detected in environmental samples based on a model-derived metric that quantifies a feature's attribute that makes it desirable to elucidate its structure, e.g., a high potential for bioaccumulation in humans or wildlife. The procedure involves the identification of isomers that could plausibly represent the molecular formulae assigned to NTA-detected chemical features. For each isomer, the prioritization metric is calculated using properties predicted with high-throughput methods. After the molecular formulae are ranked based on the average values of the prioritization metric calculated for all isomers assigned to a formula, the highest ranked molecular formulae are prioritized for structure elucidation. We applied this workflow to features identified in house dust, using the ratio of chemical intake through dust ingestion to chemical concentration in blood (dose-to-concentration ratio, DCR) as the prioritization metric. Collections of isomers for the molecular formulae were assembled from the PubChem database and DCR was estimated using partitioning and biotransformation properties predicted for each isomer using quantitative structure property relationships. The ten top-ranked molecular formulae with notably lower average DCR-values represented mostly compounds already known to be indoor pollutants of concern, such as two polybrominated diphenyl ethers, bis(2-ethylhexyl) tetrabromophthalate, tetrabromobisphenol A, tris(1,3-dichloroisopropyl)phosphate and the azo dye disperse blue 373.


The Potential Cost-Effectiveness of Pre-Exposure Prophylaxis Combined with HIV Vaccines in the United States.
This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines in development by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for the assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standard HIV prevention, daily oral PrEP, HIV vaccine, and their combination. We constructed a Markov model based on clinical trial data and the published literature. We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices, PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER = $463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. The results suggest that boosting potential may be key to HIV vaccine value.


Piezosurgery in periodontology and oral implantology.
Periodontitis is a chronic inflammatory disease of the tooth-supporting structures. The treatment of this condition is largely based on the removal of local factors and restoration of the bony architecture. Moreover, in the era of modern dentistry, successful implant therapy often requires sound osseous support. Traditionally, osseous surgery has been performed by either manual or motor-driven instruments. However, both these methods have their own advantages and disadvantages. Recently, a novel surgical approach using piezoelectric device has been introduced in the field of periodontology and oral implantology. This article discusses about the wide range of application of this novel technique in periodontology.