Distinguishing the lipid profile of GCK-MODY patients and its correlation with hsCRP levels.
Glucokinase-maturity-onset diabetes of the young (GCK-MODY) is the most common monogenic diabetes in China. We have previously reported on the low levels of high-sensitivity C-reactive protein (hsCRP) in patients with GCK-MODY. In this study, we further explored the correlation between the serum lipid profiles and hsCRP levels of patients with different types of diabetes. We also proposed to determine the possible mechanism of macrovascular protection in GCK genetic variants. The serum lipid profiles of the GCK-MODY group (n = 50) were compared with those of the hepatocyte nuclear factor-1 alpha (HNF1A)-MODY group (n = 19), the type 1 diabetes (T1D) group (n = 50), and the type 2 diabetes (T2D) group (n = 54). The associations between the lipid compositions and the hsCRP levels in each group were also explored. Elevated levels of high-density lipoprotein cholesterol (HDL-C) were found in the GCK-MODY group (1.5 ± 0.27) compared with the T1D (1.2 ± 0.47, p < 0.01) and T2D (1.3 ± 0.3, p < 0.01) groups. On the other hand, a significantly lower LDL-C level (2.4 ± 0.69) in the GCK-MODY group compared with the T1D (2.7 ± 0.72, p < 0.01) and T2D (2.9 ± 0.68, p < 0.01) groups was also noted. A lower ratio of triglyceride to HDL-C (TG/HDL) and a lower hsCRP level were also found in the GCK-MODY group [TG/HDL = 0.38 (0.25-0.52), hsCRP = 0.2 mg/L (0.16-0.37)] compared with the T1D group [(TG/HDL = 0.56 (0.39-1.29), hsCRP = 0.56 mg/L (0.39-1.29), p < 0.01] and the T2D group [(TG/HDL = 1.6 (1.1-2.68), hsCRP = 1.11 mg/L (0.66-2.34), p < 0.01]. Although patients with HNF1A-MODY showed similar hsCRP levels [0.17 (0.08-0.52), p > 0.05] compared with the patients in the GCK-MODY group, they had higher TG levels [1.01 (0.66-1.76), p < 0.05] and TG/HDL ratios [0.84 (0.56-1.31), p < 0.05]. Analysis of the correlations between the hsCRP levels and lipid profiles of each group confirmed that the LnhsCRP (natural logarithm-transformed hsCRP level) was positively correlated with the LnTG (natural logarithm-transformed TG) (r = 0.352, p = 0.011) and the Ln(TG/HDL) ratio (r = 0.283, p = 0.047) only in individuals with GCK-MODY. Individuals harboring GCK variants have the characteristics of protective lipid profiles manifested as a higher level of HDL-C and a lower level of LDL-C compared with type 1 and 2 diabetes milletus (T1DM and T2DM, respectively) patients. In addition, lower ratios of TG/HDL were found to be associated with the inhibition of secretion of hsCRP, even when adjusted for the HbA1c levels in patients with GCK-MODY. It is suggested that the protective effect of macrovascular complications in GCK-MODY patients might partly be due to their unique lipid profiles associated with the suppression of inflammation.


Surface stabilized atorvastatin nanocrystals with improved bioavailability, safety and antihyperlipidemic potential.
Atorvastatin, a favored option for hyperlipidemia exhibits the problem of poor gastric solubility and low absolute bioavailability (12%) along with higher pre-systemic clearance (>80%). Therefore, to circumvent these limitations, atorvastatin nanocrystals were prepared using poloxamer-188 as stabilizer via high pressure homogenization technique followed by lyophilization. Various variables like drug to poloxamer-188 ratio, homogenization cycle, homogenization pressure, type and concentration of cryoprotectant were optimized to achieve uniform nanosized crystals with good dispersibility. Solid state characterization by ATR-FTIR and DSC revealed no incompatible physicochemical interaction between drug and excipients in formulation while DSC and PXRD collectively corroborated the reduced crystallinity of drug in nanocrystals. Size analysis and SEM confirmed nanometric size range of nanocrystals (225.43 ± 24.36 nm). Substantial improvement in gastric solubility (~40 folds) and dissolution rate of drug in nanocrystals was observed. Pharmacokinetic study in wistar rats revealed significant improvement in oral bioavailability (~2.66 folds) with atorvastatin nanocrystals compared to pure drug. Furthermore, reduction in serum total lipid cholesterol, LDL and triglyceride content justified the effectiveness of formulation at 50% less dose of atorvastatin along with improved plasma safety profile in comparison of pure drug. In conclusion, atorvastatin nanocrystals are safe and efficacious drug delivery system confirming potent competence in treatment of hyperlipidemic conditions with ease of scalability for commercialization.


Antioxidant activities of recombinant amphioxus (Branchiostoma belcheri) apolipoprotein D.
Apolipoprotein D (ApoD), a member of lipocalin, has been recently shown to be involved in regulating protection from oxidative stress. The absence of ApoD in mouse and Drosophila can reduce the resistance to oxidative stress and shorten lifespan. However, little information is available regarding the expression in vitro of ApoD and its biochemical properties. Amphioxus (Branchiostoma belcheri) ApoD, BbApoD, is an archetype of vertebrate ApoD proteins. In this study, the prokaryotic expression plasmid pET32a-BbApoD was constructed and recombinant BbApoD expressed in Escherichia coli BL21 and purified. Antioxidation assays showed that the recombinant BbApoD protein had the capacities to scavenge hydroxyl radicals (≥ 240 μg/ml) and to prevent nicking of the supercoiled DNA (≥ 100 μg/ml) in vitro, providing a biochemical evidence for antioxidant role of ApoD. This supports the notion that ApoD is part of the mechanisms regulating protection from oxidative stresses.


[Patient satisfaction with the outcome of surgical orthodontic intervention and effect of esthetic and functional criteria].
The aim of the study was to analyze the influence of possible temporary or permanent disorders of sensation on the degree of the patient's satisfaction following an orthognathic operation. After an average of 47 months (range: 9-141), a follow-up examination was performed in 78 women (64.5%) and 43 men (35.5%) with an average age of 24.3 years (range: 19-40) at the time of operation. In 67 cases there had been a sagittal division of the mandible, in 11 cases a Le Fort I osteotomy, in 26 cases a bimaxillary osteotomy, in 4 cases an isolated genioplasty, and in 13 cases a segmental osteotomy in the upper or the lower jaw. In the peripheral area supplied by the nerves V2 and V3 sensation was examined by the two-point discrimination test and the result related to the patients' satisfaction using the chi-square test. The following qualities of sensation were recorded: anesthetic (2.7%), hypesthetic (16.6%), paresthetic (8.3%), and normesthetic (72.4%). The patients' satisfaction was rated as very satisfied in 51.3%, as satisfactory in 44.8%, and in 3.9% the patients' expectations had not been fulfilled; 75% regarded their outward appearance as markedly improved and a good 50% of the patients noted improved mastication. Therefore, three-fourths of all the patients would even be willing to be operated on again. Two-dimensional analysis, however, demonstrated only a weakly significant positive relationship between patient satisfaction and the preserved, or restored, sensation in the trigeminal region.


Mortality after uveal and conjunctival melanoma: which tumour is more deadly?
We aimed to model and compare mortality rates for uveal melanoma (UM) and conjunctival melanoma (CM) by adjusting for differences in tumour size and local recurrence. Population-based mortality data for 240 and 85 patients with primary UM and CM and 91 and 23 patients with disseminated UM and CM, respectively, were compared with cumulative incidence analysis. Cox proportional hazards multivariate regression with time-dependent variables was used to adjust for differences in tumour diameter, thickness and recurrence rates. The 10-year cumulative incidences of metastatic death from UM and CM were 39% (95% confidence interval [CI] 33-45) and 32% (95% CI 21-44), respectively. After adjusting for tumour size, risk of death from CM was higher than from UM (hazard ratio [HR] 1.9; p = 0.039). Additional adjustment for more frequent local recurrence of CM diminished the difference (HR 1.5; p = 0.25). Survival periods after systemic metastasis of UM and CM were comparable (median 8 months). Clinical observations show longer survival after primary CM than after primary UM. This reflects the smaller average size of CM. However, a primary CM of a given size is more deadly than a UM of equivalent size because primary CM tends to recur after treatment and, possibly, because additional lymphatic dissemination occurs with CM.


Sea-lice infection models for fishes.
As free-living sea-lice larvae are difficult to sample directly, lice abundances on fish have recently been used to study larvae in the water. In the KLV problem, juvenile wild salmon migrate past a salmon farm, and the change of infection with distance along the migration route is used to estimate larvae production from the farm. In the farm problem, time-varying infection of sea-cage fish is used to estimate the time-variation of free-living larvae in waters near the farm. Both inverse problems require good forward models for infection. In the farm problem, hosts are relatively large and lice pathogenesis is seldom mortal, whereas in the KLV problem hosts are small and lice-induced host mortality can affect lice abundance; thus, infection models for the farm problem are special cases of models for the KLV problem. Here I give an infection model for the KLV problem that explicitly includes lice clumping and host mortality, showing that Krkosek et al. (Proc R Soc B 272:689-696, 2005) (KLV) probably underestimated larvae production by the salmon farm, and further, that if lice development rates were known from laboratory data, lice abundance field data could be directly inverted for lice-induced host mortality during migration. If lice-induced host mortality is negligible, or if lice are Poisson distributed, infection models of arbitrary complexity reduce to Erlang models. I give two useful Erlang models with their solutions for non-zero initial conditions.


Dentistry in the People's Republic of China with particular reference to gerodontology.
The People's Republic of China is increasingly becoming open to the West, and a number of visits have recently been, and are about to be, made by British dentists. In November 1988, the authors of this report made a 2-week lecture tour, under the auspices of the Health Co-operation Agreement between the Department of Health (UK) and the Chinese Ministry of Public Health, organised by the British Council. The principal base for the visit was the Institute of Geriatrics at the Beijing Hospital, where seven lectures were given. Further lectures and seminars were given to staff and postgraduate students at the Fourth Military University in Xian.


Elevated Lipoprotein(a) does not promote early atherosclerotic changes of the carotid arteries in young, healthy adults.
Elevated levels of Lipoprotein(a) [Lp(a)] have been linked to an increased risk of ischemic cardiovascular events. Yet the mechanism by which Lp(a) might contribute to this increased risk is not clear. To elucidate whether high plasma levels of Lp(a) contribute to the development of early atherosclerotic vessel wall changes, the intima-media thickness of the common carotid arteries [CCA-IMT] of 151 healthy young volunteers without additional relevant cardiovascular risk factors was measured by high-resolution ultrasound. Plasma concentrations of Lp(a) were quantified and other established risk factors, such as body mass index [BMI], plasma levels of cholesterol, triglycerides and homocysteine, were determined. Furthermore, the carotid arteries were examined for the presence of plaques and stenoses. Univariate analysis showed a significantly negative correlation of CCA-IMT with HDL cholesterol and positive correlations with age, BMI, total and LDL cholesterol, triglycerides and even with homocysteine, but not with Lp(a). When the study population was dichotomized according to Lp(a) levels, no statistically significant differences in CCA-IMT could be detected between persons with plasma Lp(a)<300mg/l or >or=300mg/l, respectively. Our data suggest that elevated Lp(a) levels alone do not contribute to increased cardiovascular risk by promoting early atherogenesis in vivo.


College students' experiences of sexual violence and reasons for seeking care in campus health and counseling centers.
Examine associations between care seeking reasons in college health and counseling centers and sexual violence (SV). College students (n = 2,084 baseline, n = 1,170 one-year follow up) participating in a cluster randomized controlled trial of an SV reduction intervention on 28 campuses. Computer-based survey data gathered during students' clinic visit and one-year follow up. Despite high prevalence of SV, students almost never sought care specifically for SV (0.5% of reported visits). Gender differences emerged for reasons students sought care generally, but were not associated with differences in care seeking among those who experienced SV. At baseline and one-year, students who reported SV were more likely to state mental or sexual and reproductive health as their reason for care seeking. Many students seeking care have experienced SV yet present with other health needs. Providers need to recognize this and have a low threshold for providing SV resources routinely.


The effect of raising the scala tympani potassium concentration on the tone-induced cochlear responses of the guinea pig.
Scala tympani (ST) in guinea pig was perfused with modified Ringer's solutions containing 5--50 mM potassium; tone-induced cochlear responses from the basal turn of ST were compared before, during and after perfusions. The compound nerve action potential (N1) and afterpotential (a/p) amplitudes were reduced, especially above 20 mM; the summating potential (SP) was variable, but its onset shape changed consistently with 13--20 mM levels. However, the cochlear microphonic amplitude (CM) remained substantially unchanged even at the 35 mM level. K+ concentration was monitored in ST with ion-sensitive pipettes. Stable levels were reached within 2 min, but N1 responses continued to fall beyond this time. Recovery to normal K+ levels took place spontaneously and the concentration curve which resulted showed a 2-slope characteristic. These experiments question whether elevated potassium concentration in scala tympani depolarizes the hair cells, and if it does, whether the hear cell resting potential is involved in the generation of the CM.


Glutamate and GABA synthesis, release, transport and metabolism as targets for seizure control.
The synthesis, release, reuptake, and metabolism of the excitatory and inhibitory neurotransmitters glutamate and GABA, respectively, are tightly controlled. Given the role that these two neurotransmitters play in normal and abnormal neurotransmission, it is important to consider the processes whereby they are regulated. This brief review is focused entirely on the metabolic aspects of glutamate and GABA synthesis and neurotransmission. It describes in limited detail the synthesis, release, reuptake, metabolism, cellular compartmentation and pharmacology of the glutamatergic and GABAergic synapse. This review also provides a summary and brief description of the pathologic and phenotypic features of the various genetic animal models that have been developed in an effort to provide a greater understanding of the role that each of the aforementioned metabolic processes plays in controlling excitatory and inhibitory neurotransmission and how their use will hopefully facilitate the development of safer and more efficacious therapies for the treatment of epilepsy and other neurological disorders.


Association between a serotonin transporter promoter region polymorphism and mood response during tryptophan depletion.
This study investigated the relationship between depressive symptom response during tryptophan (TRP) depletion and a functional polymorphism of the promoter region of the serotonin (5-HT) transporter gene (SLC6A4).(1) Forty-three subjects in remission from a major depressive episode who underwent TRP depletion were genotyped. DNA was extracted from blood lymphocytes or from cheek cells.(2) The two common alleles are designated long (l) and short (s). Depressive symptoms were measured with the 25-item Hamilton Depression Rating Scale (HDRS).(3) There was a significant association between the l homozygous genotype and the depressive response to TRP depletion, with a significant main effect of time (F = 8.763, df = 3, 38, P = <0.001), and time x l homozygous allele interaction (F = 3.676, df = 3, 38, P = 0.02). Individuals whose genotype predicted increased 5-HT transporter activity may be more susceptible to depressive changes in response to transient 5-HT perturbations. The use of endophenotypic markers for affective disorders such as the mood response to TRP depletion may facilitate studies of complex genetic traits such as depression by decreasing its heterogeneity.


Splenic infarction as a rare complication of infectious mononucleosis due to Epstein-Barr virus infection in a patient with no significant comorbidity: case report and review of the literature.
We report the case of a 17-y-old boy diagnosed with infectious mononucleosis due to Epstein-Barr virus infection who complained of left upper quadrant pain. A magnetic resonance imaging scan showed a splenic infarct in the enlarged spleen. Other causes of splenic infarction were excluded. Thus, infectious mononucleosis may cause splenic infarction in patients without other comorbidities.


Venous thoracic outlet syndrome.
Venous thoracic outlet syndrome is caused by subclavian vein obstruction with or without thrombosis. The primary symptom is arm swelling, frequently accompanied by cyanosis, pain, and occasionally paresthesias. Venography is the only reliable diagnostic tool. Therapy has three goals: (1) remove the thrombus (in thrombotic cases), (2) remove the extrinsic compression, and in a minority of cases, (3) remove the intrinsic stenosis.


Spin biochemistry: magnetic 24Mg-25Mg-26Mg isotope effect in mitochondrial ADP phosphorylation.
The rates of adenosine triphosphate (ATP) production by isolated mitochondria and mitochondrial creatine kinase incubated in isotopically pure media containing, separately, (24)Mg(2+), (25)Mg(2+), and (26)Mg(2+) ions were shown to be strongly dependent on the magnesium nuclear spin and magnetic moment. The rate of adenosine 5'-diphosphate phosphorylation in mitochondria with magnetic nuclei (25)Mg is about twice higher than that with the spinless, nonmagnetic nuclei (24,26)Mg. When mitochondrial oxidative phosphorylation was selectively blocked by treatment with 1-methylnicotine amide, (25)Mg(2+) ions were shown to be nearly four times more active in mitochondrial ATP synthesis than (24,26)Mg(2+) ions. The rate of ATP production associated with creatine kinase is twice higher for (25)Mg(2+) than for (24,26)Mg and does not depend on the blockade of oxidative phosphorylation. There is no difference between (24)Mg(2+) and (26)Mg(2+) effects in both oxidative and substrate phosphorylation. These observations demonstrate that the enzymatic phosphorylation is a nuclear spin selective process controlled by magnetic isotope effect. The reaction mechanism proposed includes a participation of intermediate ion-radical pairs with Mg(+) cation as a radical partner. Therefore, the key mitochondrial phosphotransferases work as a magnesium nuclear spin mediated molecular machines.


Development and validation of prediction model using nursing notes on sentiment scores for prognosis of patients with severe acute kidney injury receiving continuous renal replacement therapy based on computational intelligence algorithms.
Currently, the prediction values of models for the prognosis of acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT) were ordinary and establishing a better prediction model is necessary. Nursing notes are an important predictor of in-hospital mortality in intensive care unit (ICU) patients. This study established prognostic prediction models for AKI patients receiving CRRT especially using nursing notes. Totally, 682 AKI patients undergoing CRRT were included. AKI was diagnosed based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Four hundred and twelve patients lacking nursing notes data were excluded. Finally, 270 patients were included and randomly divided into a training set (n=189) and a testing set (n=81) at a ratio of 7:3. Univariate analysis explored the possible predictors of mortality in AKI patients receiving CRRT. Random forest models and broad learning system (BLS) models (with or without sentiment scores) were respectively constructed in the training set and verified in the testing set. The performances of the models were assessed by the sensitivity, specificity, and area under the curve (AUC). For the random forest model including the sentiment scores, the AUC was 0.86 (95% CI: 0.81-0.91), the sensitivity was 0.72 (95% CI: 0.63-0.80), and the specificity was 0.87 (95% CI: 0.80-0.94) in the training set and the AUC was 0.78 (95% CI: 0.68-0.88), the sensitivity was 0.65 (95% CI: 0.49-0.80), and the specificity was 0.75 (95% CI: 0.62-0.88) in the testing set. For the BLS model including the sentiment scores, the AUC was 0.87 (95% CI: 0.82-0.92), the sensitivity was 0.95 (95% CI: 0.91-0.99) and the specificity was 0.48 (95% CI: 0.38-0.59) in the training set and the AUC was 0.82 (95% CI: 0.73-0.91), the sensitivity was 0.41 (95% CI: 0.25-0.56) and the specificity was 0.98 (95% CI: 0.93-1.00) in the testing set. The BLS models including the sentiment scores might offer a tool for quickly identifying patients AKI patients receiving CRRT with high risk of mortality and providing timely interventions to them for improving their prognosis.


Follicular thyroid carcinoma with predominantly cystic formation presenting initially with multiple distant metastases.
Primary malignancies presenting with multiple distant metastases include lung cancer, gastrointestinal malignancy, breast cancer, and prostatic cancer. Multiple distant metastases from follicular thyroid carcinoma (FTC) are uncommon. Cystic formation in FTC is an atypical finding in ultrasonography. The cystic formation of a thyroid nodule is usually considered a benign sonographic finding. We report the case of a 78-year-old man who presented with multiple distant metastases from an FTC with a predominantly cystic formation.


Melatonin attenuates morphine-induced conditioned place preference in Wistar rats.
Morphine is the predominantly used drug for postoperative and cancer pain management. However, the abuse potential of morphine is the primary disadvantage of using opioids in pain management. Melatonin is a neurohormone synthesized in the pineal gland and is involved in circadian rhythms in mammals, as well as other physiological functions. Melatonin provenly attenuates alcohol-seeking and relapse behaviors in rats. Therefore, we aimed to investigate the involvement of the melatonergic system in attenuating morphine dependence. Male Wistar rats were divided into three groups: control, morphine, and morphine + melatonin. Animals were habituated for 3 days, and the initial preference was evaluated. Following the initial preference, the control group received the vehicle and was placed for a 45-min session in the assigned chamber every day, alternating between the two chambers, for 8 days. The morphine group received a morphine injection (5 mg/kg, IP) and was placed for a 45-min session in the white chamber, for a total of four sessions. The morphine + melatonin group received the morphine injection (5 mg/kg, IP) for a total of four sessions over an 8-day period. In the posttest session, the control and morphine groups received a vehicle injection 30 min before placement in the conditioned place preference (CPP). The morphine + melatonin group received a single injection of melatonin (50 mg/kg, IP) 30 min before the preference test. Statistical analysis revealed that repeated administration of morphine for four sessions produced a significant increase in the CPP score in the morphine group compared to the control group. However, a single melatonin injection administered 30 min before the posttest attenuated morphine-seeking behavior and reduced morphine-induced place preference. These findings provide novel evidence for the role of the melatonergic system as a potential target in modulating morphine-seeking behavior.


Characteristic Sounds Facilitate Object Search in Real-Life Scenes.
Real-world events do not only provide temporally and spatially correlated information across the senses, but also semantic correspondences about object identity. Prior research has shown that object sounds can enhance detection, identification, and search performance of semantically consistent visual targets. However, these effects are always demonstrated in simple and stereotyped displays that lack ecological validity. In order to address identity-based cross-modal relationships in real-world scenarios, we designed a visual search task using complex, dynamic scenes. Participants searched for objects in video clips recorded from real-life scenes. Auditory cues, embedded in the background sounds, could be target-consistent, distracter-consistent, neutral, or just absent. We found that, in these naturalistic scenes, characteristic sounds improve visual search for task-relevant objects but fail to increase the salience of irrelevant distracters. Our findings generalize previous results on object-based cross-modal interactions with simple stimuli and shed light upon how audio-visual semantically congruent relationships play out in real-life contexts.


Increasing Role of the Advanced Practice Provider in Men's Health Clinics: An Analysis of Medicare and Commercial Claims in the United States.
As urological care delivery in the U.S. continues to evolve to meet patient needs, we aim to clarify the role of advanced practice providers for publicly and privately insured patients in the treatment of male urological conditions commonly encountered in men's health clinics. Medicare and commercial insurance claims from the Physician/Supplier Procedure Summary and Merative MarketScan Commercial Database were queried for procedures submitted by advanced practice providers between 2010 and 2021. Common urological conditions were identified using Current Procedural Terminology codes and grouped into 4 categories: testicular hypofunction, erectile dysfunction and Peyronie's disease, benign prostatic hyperplasia, and scrotal pain. The proportion of procedures submitted by advanced practice providers was calculated for each year and category. From 2010 to 2021, the proportion of advanced practice provider-submitted service counts for each condition within the MarketScan group increased up to 5-fold, with benign prostatic hyperplasia representing the greatest growth. The proportion of advanced practice provider-submitted service counts within the Medicare group increased up to 8-fold, with erectile dysfunction/Peyronie's disease representing the greatest fold change. The proportion of claims submitted by advanced practice providers treating all 4 conditions was higher in 2021 than 2010 in both publicly and privately insured groups. The role of advanced practice providers in men's urological health is increasing for both privately and publicly insured patient populations. Advanced practice providers play a critical role in urological care and can help to improve access to men's health.


Delirium in the critically ill patient.
Delirium is an acute and transient brain dysfunction that is characterized by disturbances in consciousness, affecting both its content (i.e., attention) and level (i.e., arousal). It affects as many as 50% of those admitted to an intensive care unit (ICU). Once believed to be an inconsequential outcome of critical illness, it is now recognized that delirium is harmful in both the short- and long-term. Despite occurring frequently in critically ill patients, delirium often goes unrecognized. Well-validated delirium screening tools, designed for use in the ICU, should be used to reliably detect delirium. The first step in delirium treatment is to identify and address potentially modifiable risk factors. Multiple trials have shown that benzodiazepines are a risk factor for delirium in a dose-dependent manner. Sedation with nonbenzodiazepine-based strategies are an effective means by which to reduce delirium. Nonpharmacologic strategies such as those which seek to reduce sensory impairment, sleep deprivation, and immobility are effective. Pharmacologic treatment with antipsychotics, though commonly used, is not supported by findings from placebo-controlled trials. Recent data support from multiple trials support the use of the "ABCDEF bundle" as a means by which to reduce delirium.


Dermatological Conditions of the Breast.
There are many dermatologic conditions that can involve the skin of the breast including malignancy, infections, and inflammatory conditions. These are summarized here including presentation and management options.


[The practical application of computer dosimetry in gynaecological radiotherapy. 1,200 cases studied between 1968 and 1976 of the Gustave-Roussy institute (author's transl)].
Experience gained since 1970 by the study of 1,200 cases in which computerised dosimetry was used has led to the proposition of a reliable and useful method. The results are expressed per 24 hours of exposure in numerical form with regard to reference points, as well as in the form of drawn isodose curves in three different planes of reference: sagittal, frontal oblique by sources and frontal oblique passing by the plane of pelvic lymphatics. The authers recall the definition of reference points: bladder, rectum and pelvic walls. Using three typical examples, the aid provided by dosimetry is described. The concept of a "radiotherapy identity card" as a means of expressing the dose given is discussed. Comparison between dosimetric results and the results of treatment is encouraging in terms of the continued and fore general use of the method.


Computer-assisted midface reconstruction in Treacher Collins syndrome part 2: soft tissue reconstruction.
Treacher Collins syndrome (TCS) midfacial involvement associate a skeletal hypoplasia centred on the zygoma to a hypoplasia of all surrounding soft tissues layers and an inferolateral lower lid pseudocoloboma. TCS soft tissue hypoplasia, which has not been well studied, continues to bring challenges in both the indication of surgical treatment and the prediction of their results. From a standard magnetic resonance imaging (MRI) acquisition, we studied qualitatively and quantitatively the prezygomatic fat compartments and the buccal fat pad of two individuals with TCS whose age were 10 and 14 years. In parallel, we studied 20 controls at the same age to obtain a morphometric database of reference and compare our results. TCS soft tissue involvement was correlated to the results of our prior skeletal involvement study. The midfacial fat compartments in TCS are severely hypoplastic, especially in the superficial and lateral compartments of the face (all P's < 0.001). No significant correlation existed between the soft tissue and the skeletal involvement. To our knowledge, this is the first published study of TCS midfacial fat compartments. Their hypoplasia is an important part of the syndrome's facial deformity. The knowledge of their anatomy, organization and volumetric variation is essential. Their re-establishment is key in the early treatment phases of this syndrome. Using the preoperative data, the morphometric database of reference, and surgical simulation, an appropriate surgical technique, going from an autologous fat graft to a free flap, can then be chose.


Development of a bis-pyrene phospholipid probe for fluorometric detection of phospholipase A2 inhibition.
In this work, we report the design, synthesis, and application of a bis-pyrene phospholipid probe for detection of phospholipase A2 action through changes in pyrene monomer and excimer fluorescence intensities. Continuous fluorometric assays enabled detection of the activities of multiple PLA2 enzymes as well as the decrease in catalysis by PLA2 from honey bee venom caused by the inhibitor p-bromo phenacylbromide. Thin-layer chromatography and mass spectrometry analysis were also used to validate probe hydrolysis by PLA2. Mass spectrometry data also supported cleavage of the probe by phospholipase C and D enzymes, although changes in fluorescence were not observed in these cases. Nevertheless, the bis-pyrene phospholipid probe developed in this work is effective for detection of PLA2 enzyme activity through an assay that enables screening for inhibitor development.


Prediction and probability of neonatal outcome in isolated congenital diaphragmatic hernia using multiple ultrasound parameters.
To evaluate the accuracy and probabilities of different fetal ultrasound parameters to predict neonatal outcome in isolated congenital diaphragmatic hernia (CDH). Between January 2004 and December 2010, we evaluated prospectively 108 fetuses with isolated CDH (82 left-sided and 26 right-sided). The following parameters were evaluated: gestational age at diagnosis, side of the diaphragmatic defect, presence of polyhydramnios, presence of liver herniated into the fetal thorax (liver-up), lung-to-head ratio (LHR) and observed/expected LHR (o/e-LHR), observed/expected contralateral and total fetal lung volume (o/e-ContFLV and o/e-TotFLV) ratios, ultrasonographic fetal lung volume/fetal weight ratio (US-FLW), observed/expected contralateral and main pulmonary artery diameter (o/e-ContPA and o/e-MPA) ratios and the contralateral vascularization index (Cont-VI). The outcomes were neonatal death and severe postnatal pulmonary arterial hypertension (PAH). Neonatal mortality was 64.8% (70/108). Severe PAH was diagnosed in 68 (63.0%) cases, of which 63 died neonatally (92.6%) (P < 0.001). Gestational age at diagnosis, side of the defect and polyhydramnios were not associated with poor outcome (P > 0.05). LHR, o/e-LHR, liver-up, o/e-ContFLV, o/e-TotFLV, US-FLW, o/e-ContPA, o/e-MPA and Cont-VI were associated with both neonatal death and severe postnatal PAH (P < 0.001). Receiver-operating characteristics curves indicated that measuring total lung volumes (o/e-TotFLV and US-FLW) was more accurate than was considering only the contralateral lung sizes (LHR, o/e-LHR and o/e-ContFLV; P < 0.05), and Cont-VI was the most accurate ultrasound parameter to predict neonatal death and severe PAH (P < 0.001). Evaluating total lung volumes is more accurate than is measuring only the contralateral lung size. Evaluating pulmonary vascularization (Cont-VI) is the most accurate predictor of neonatal outcome. Estimating the probability of survival and severe PAH allows classification of cases according to prognosis.


Prednisolone exerts exquisite inhibitory properties on platelet functions.
We have previously reported presence of the glucocorticoid (GC) receptor (GR) alpha on blood platelets, and its ability to modulate platelet aggregation when activated by the synthetic GC prednisolone (Pred). In the present study we investigated the effects of Pred on broader aspects of platelet functions to unveil novel non-genomic actions on this cell type. Using whole blood assay we demonstrated that Pred was the only GC able to inhibit platelet aggregation and platelet-monocyte interactions. This latter effect was due to regulation of platelets, not monocytes. We next examined the effects of Pred on physiological actions of platelets, observing inhibition of platelet adhesion and spreading on collagen under static conditions. Moreover Pred inhibited thrombus formation under flow, suggesting potential important effects in haemostasis and thrombosis. Pred was unable to regulate platelet reactivity under conditions where the effects of platelet-derived ADP and TxA₂ were blocked, suggesting that the GC targeted the activation-dependent component of the adhesion and aggregation response. The effects of Pred were not mediated through cyclic nucleotide signaling, but rather seemed to evolve around selective regulation of P2Y₁₂ ADP receptor signaling, intimating a novel mode of action. This study details the actions of Pred on platelets unveiling novel properties which could be relevant for this GC in controlling unwanted vascular and thrombotic diseases.


Effect of oral contraceptives on energy balance in women: A review of current knowledge and potential cellular mechanisms.
Body weight management is currently of major concern as the obesity epidemic is still a worldwide challenge. As women face more difficulties to lose weight than men, there is an urgent need to better understand the underlying reasons and mechanisms. Recent data have suggested that the use of oral contraceptive (OC) could be involved. The necessity of utilization and development of contraceptive strategies for birth regulation is undeniable and contraceptive pills appear as a quite easy approach. Moreover, OC also represent a strategy for the management of premenstrual symptoms, acne or bulimia nervosa. The exact impact of OC on body weight remains not clearly established. Thus, after exploring the potential underlying mechanisms by which OC could influence the two side of energy balance, we then provide an overview of the available evidence regarding the effects of OC on energy balance (i.e. energy expenditure and energy intake). Finally, we highlight the necessity for future research to clarify the cellular effects of OC and how the individualization of OC prescriptions can improve long-term weight loss management.


Fast, sensitive point of care electrochemical molecular system for point mutation and select agent detection.
Point of care molecular diagnostics benefits from a portable battery-operated device capable of performing a fast turnaround using reliable inexpensive cartridges. We describe a prototype device for performing a molecular diagnostics test for clinical and biodefense samples in 16 minutes using a prototype capable of an 8 minute PCR reaction, followed by hybridization and detection on an electrochemical microarray based on the i-STAT® system. We used human buccal swabs for hemochromatosis testing including in-device DNA extraction. Additional clinical and biodefense samples included influenza A and bacterial select agents Bacillus anthracis, Yersinia pestis and Francisella tularensis.


The Good, The Bad, and The Distant: Soundscape Cues for Larval Fish.
Coral reef noise is an important navigation cue for settling reef fish larvae and can thus potentially affect reef population dynamics. Recent evidence has shown that fish are able to discriminate between the soundscapes of different types of habitat (e.g., mangrove and reef). In this study, we investigated whether discernible acoustic differences were present between sites within the same coral reef system. Differences in sound intensity and transient content were found between sites, but site-dependent temporal variation was also present. We discuss the implications of these findings for settling fish larvae.


5-Ethynyluracil (776C85): inactivation of dihydropyrimidine dehydrogenase in vivo.
5-Ethynyluracil (776C85), a potent, mechanism-based, irreversible inactivator (Porter et al., J Biol Chem 267:5236-5242, 1992) of purified dihydropyrimidine dehydrogenase (DPD, uracil reductase, EC 184.108.40.206), readily inactivated DPD in vivo. DPD was assayed in tissue extracts by measuring the release of 14CO2 from [2-14C]uracil with an improved method. Specific activities from 0.1 to > 1000 U/mg protein were reproducibly measured. After rats were orally dosed with 20 micrograms/kg 5-ethynyluracil, liver, intestinal mucosa, lung, and spleen DPD were inactivated by 83-94%. The dose required to inactivate rat liver, rat brain, and mouse liver DPD by 50% was 1.8, 11, and 8.9 micrograms/kg, respectively. Rat liver DPD was inactivated completely within 25 min after an oral dose of 500 micrograms/kg 5-ethynyluracil. New DPD was synthesized with a half-time of 63 hr. We also developed an assay based on stoichiometric inactivation of DPD by 5-ethynyluracil to measure 5-ethynyluracil in plasma samples. Samples containing 5-ethynyluracil were incubated with rat liver extract for 24 hr at 12 degrees and then assayed for DPD. DPD activity decreased linearly with the concentration of 5-ethynyluracil (between 0 and 20 nM 5-ethynyluracil). The assay could detect 5-ethynyluracil at concentrations as low as 6 nM in human plasma and was not affected by high concentrations of uracil.


Acoustically induced coherent spin trapping.
Spin centers are promising qubits for quantum technologies. Here, we show that the acoustic manipulation of spin qubits in their electronic excited state provides an approach for coherent spin control inaccessible so far. We demonstrate a giant interaction between the strain field of a surface acoustic wave (SAW) and the excited-state spin of silicon vacancies in silicon carbide, which is about two orders of magnitude stronger than in the ground state. The simultaneous spin driving in the ground and excited states with the same SAW leads to the trapping of the spin along a direction given by the frequency detuning from the corresponding spin resonances. The coherence of the spin-trapped states becomes only limited by relaxation processes intrinsic to the ground state. The coherent acoustic manipulation of spins in the ground and excited state provides new opportunities for efficient on-chip quantum information protocols and coherent sensing.


The planktonic protist interactome: where do we stand after a century of research?
Microbial interactions are crucial for Earth ecosystem function, but our knowledge about them is limited and has so far mainly existed as scattered records. Here, we have surveyed the literature involving planktonic protist interactions and gathered the information in a manually curated Protist Interaction DAtabase (PIDA). In total, we have registered ~2500 ecological interactions from ~500 publications, spanning the last 150 years. All major protistan lineages were involved in interactions as hosts, symbionts (mutualists and commensalists), parasites, predators, and/or prey. Predation was the most common interaction (39% of all records), followed by symbiosis (29%), parasitism (18%), and 'unresolved interactions' (14%, where it is uncertain whether the interaction is beneficial or antagonistic). Using bipartite networks, we found that protist predators seem to be 'multivorous' while parasite-host and symbiont-host interactions appear to have moderate degrees of specialization. The SAR supergroup (i.e., Stramenopiles, Alveolata, and Rhizaria) heavily dominated PIDA, and comparisons against a global-ocean molecular survey (TARA Oceans) indicated that several SAR lineages, which are abundant and diverse in the marine realm, were underrepresented among the recorded interactions. Despite historical biases, our work not only unveils large-scale eco-evolutionary trends in the protist interactome, but it also constitutes an expandable resource to investigate protist interactions and to test hypotheses deriving from omics tools.


Domain structure of the 90-kDa stress protein: heparin- and antibody-binding domain.
1. To understand the physiological roles of the 90-kDa stress protein (HSP90), we investigated the heparin- and antibody-binding domains of the protein. 2. For heparin-binding sites, HSP90 was digested completely with trypsin, and the digests were applied to a heparin-Sepharose column and eluted with 1.0 M NaCl, followed by 8.0 M urea. 3. Each elutant was purified by a reverse-phase C18 column. 4. Two peptides from the NaCl-eluted fraction and no peptide from the urea-eluted fraction were purified. 5. The purified peptides were sequenced by an automated peptide sequencer. 6. One of the heparin-binding sites was present between Leu-362 and Arg-365; another was present between Leu-645 and Lys-648. 7. These two peptides were basic and considerably hydrophilic. 8. For antibody-binding sites, HSP90 was mildly digested with trypsin, electrophoresed on SDS-polyacrylamide gels and transferred to PVDF membranes. 9. The four bound of the trypsin fragments could be sequenced with a peptide sequencer. 10. There was only one antibody-binding peptide, 38 kDa, starting from Pro-2. The others showed no cross-reactivity with the antibody and started from Leu-283. 11. Therefore, the epitopes of HSP90 are present between Pro-2 and Leu-282. 12. The heparin-binding sites are present from the middle region of the HSP90 molecule, and the antigen sites are at the N-terminal domain.


A novel prognosis-prediction model based on coagulation indicators in secondary hemophagocytic lymphohistiocytosis.
Secondary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. In the present retrospective study, we aimed to investigate coagulation disorders and their outcome implications in patients with secondary HLH. We evaluated clinical characteristics and the relationship between coagulation indices and prognosis in HLH patients (n = 141). The information, including clinical symptoms, laboratory indicators, and coagulation indices, was evaluated. Coagulation disorders and bleeding events occurred in 95 (67.4%) and 60 (42.6%) patients, respectively. A coagulation index analysis primarily showed elevated levels of D-Dimer, the international standardized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT), while the prothrombin activity, fibrinogen levels, and platelet levels were significantly decreased. Dominant disseminated intravascular coagulation (DIC) occurred in 76 patients (53.9%). Patients with lymphoma-associated hemophagocytic syndrome (LAHS) frequently exhibited apparent coagulation disorders. Multivariate analysis revealed that age ≥ 29.5 years, bleeding events, APTT ≥ 47.3 s, fibrinogen ≤ 1.68 g/L, and absolute neutrophil counts (ANC) of ≤ 1.21 × 109/L were independent prognostic factors. We thereby devised a prognostic scoring system and stratified patients into low-risk (0-2 points), intermediate-risk (3-4 points), and high-risk (5-7 points) groups, and the 1-year overall survival rates in the above-mentioned groups were 66.40%, 40.00%, and 2.30%, respectively (P < 0.0001). In conclusion, coagulation dysfunctions and bleeding tendencies were common characteristics in HLH patients. We constructed a novel prognostic score model based on APTT, fibrinogen level, ANC, age, and bleeding events, which had superior prognostic value compared with these markers alone.


Synthesis of dinucleoside tetraphosphates in transfected cells by a firefly luciferase reporter gene.
The firefly luciferase gene is widely used as a reporter gene and its expression is generally considered to be non-toxic. In addition to its light-producing reaction, luciferase can synthesise dinucleoside polyphosphates, intracellular signalling molecules, in vitro. Here we show that COS-7 cells transfected with a luciferase expression vector accumulate up to 0.5 mM adenine-containing dinucleoside tetraphosphates (Ap4N) during the 24 h following luciferin addition. The optimal external concentration of luciferin was 0.4-0.6 mM. In agreement with its poor ability to synthesise adenine-containing dinucleoside triphosphates in vitro, the level of these compounds did not increase after transfection. Consequently, the results of experiments involving luciferase-mediated light production by live cells should now be viewed in the light of the possible effects of an increased intracellular Ap4N concentration on the properties of the system under investigation. This observation also points to a useful non-invasive procedure for the specific enhancement of intracellular Ap4N for studies directed at understanding the functions of these compounds.


Efficacy and Safety of Lyophilized Articular Cartilage Matrix as an Injectable Facial Filler.
To evaluate the efficacy and safety of an injectable lyophilized articular cartilage matrix (LACM) which is in the form of cartilage powder that may increase the convenience of use and become unaffected by donor site morbidity as a potential filler. The safety test was conducted using 20 rabbits with an intravascular embolization model. Commonly used commercial hyaluronic acid (HA), acellular dermal matrix (ADM), polymethyl methacrylate (PMMA), and polylactic acid (PLA) products were selected for comparison of efficacy and adverse effect of LACM. The efficacy test was performed using 30 mice subcutaneous buttock-injection model. Gross assessments of the changes in size of injected materials and histological examinations were conducted. Regarding the safety test, in one rabbit in the HA group, complete blurring occurred in the left eye, and necrosis of the posterior auricular artery was observed in one rabbit in the ADM group. In the ADM, severe ecchymosis around the injection sites was observed, and the bruises lasted longer than in the other groups. The LACM exhibited faster bruise resolution. Comparing the changes in size between weeks 4 and 12 in the mouse model, no significant changes in size were observed in the LACM (p = 0.359), HA (p = 0.421), and ADM (p = 0.097), but a significant change was observed in the PMMA (p = 0.001). In the histological examination, LACM exhibited well-demarcated margins with good biocompatibility. The LACM shows potential as a facial filler according to the in vivo safety and efficacy tests LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals.
High sodium intake is associated with obesity and insulin resistance, and high extracellular sodium content may induce systemic inflammation, leading to cardiovascular disease. In this study, we aim to investigate whether high tissue sodium accumulation relates with obesity-related insulin resistance and whether the pro-inflammatory effects of excess tissue sodium accumulation may contribute to such association. In a cross-sectional study of 30 obese and 53 non-obese subjects, we measured insulin sensitivity determined as glucose disposal rate (GDR) using hyperinsulinemic euglycemic clamp, and tissue sodium content using 23Na magnetic resonance imaging. Median age was 48 years, 68% were female and 41% were African American. Median (interquartile range) BMI was 33 (31.5, 36.3) and 25 (23.5, 27.2) kg/m2 in the obese and non-obese individuals, respectively. In obese individuals, insulin sensitivity negatively correlated with muscle (r = -0.45, p = 0.01) and skin sodium (r = -0.46, p = 0.01). In interaction analysis among obese individuals, tissue sodium had a greater effect on insulin sensitivity at higher levels of high-sensitivity C-reactive protein (p-interaction = 0.03 and 0.01 for muscle and skin Na+, respectively) and interleukin-6 (p-interaction = 0.024 and 0.003 for muscle and skin Na+, respectively). In interaction analysis of the entire cohort, the association between muscle sodium and insulin sensitivity was stronger with increasing levels of serum leptin (p-interaction = 0.01). Higher muscle and skin sodium are associated with insulin resistance in obese patients. Whether high tissue sodium accumulation has a mechanistic role in the development of obesity-related insulin resistance through systemic inflammation and leptin dysregulation remains to be examined in future studies. gov registration: NCT02236520.


[Cephalometric analysis of the relationship between occlusal plane and sagittal position of the mandible].
To investigate the relationship between occlusal plane and sagittal position of the mandible by examining dental and skeletal morphologies of average angle patients for better understanding of etiologies and definitive clinical guidelines of mandibular malpositions. The lateral cephalograms of 114 female average angle patients with neutral maxillary positions were selected and divided into three groups according to sagittal mandibular positions (ANB angle). Twenty-five skeletal and dental measurements were compared. The correlations between skeletal and dental measurements were analyzed by rectilinear correlation. Cant of posterior occlusal plane (OP-P) and height of the upper second molar were significantly related to sagittal position of the mandible (P < 0.05). Height of the upper second molar was relatively inadequate and OP-P was sloped when the mandible was positioned posteriorly; conversely, height of the upper second molar was excessive and OP-P tended to be flat when the mandible was positioned anteriorly. Tooth axial inclinations were affected by sagittal position of the mandible. Maxillary teeth proclined distally and mandibular ones mesially for patients with retrognathia. On the other hand, maxillary teeth proclined mesially while mandibular ones distally for patients with prognathia. There was a definite relationship between cant of posterior occlusal plane and sagittal position of the mandible in average angle patients, consistent with the dental morphologies of different skeletal configurations. In treating malocclusions of sagittal discrepancy of mandible, the height of posterior teeth and cant of OP-P might be a primary concern.


[HIV testing among women in delivery rooms in Lubumbashi, Democratic Republic of the Congo: a catch-up strategy for prevention of mother-to-child transmission].
Although HIV testing is offered during antenatal care, the proportion of women giving birth without knowing their HIV status is still important in DR Congo. The objective of this study was to determine the acceptability of rapid HIV testing among parturients in labor room, and to identify factors that are associated with the acceptability of HIV testing. Intervention including rapid HIV testing among pregnant women in labor rooms in Lubumbashi for 5 months, from September 2010 to February 2011. Pregnant women who tested HIV positive were attended by prevention of mother-to-child transmission service. Descriptive statistical analysis and logistic regression were performed. Among 474 pregnant women who enter the labor room, 433 (91.4%; confidence interval [CI]: 95%: 88.4-93.7%) had voluntary testing for HIV in the labor room after counseling. The acceptance of rapid testing for HIV was significantly higher when the duration of counseling was less or equal to 5 minutes (adjusted Odds ratio [aOR]=5.8; [CI] 95%: 2.6-13); among those who did not report having this screening test during antenatal care (aOR=3.8; [CI] 95%: 2-7.8), among those who were in early labor (aOR=2.3; [CI] 95%: 1.2-4.7) and lower in adolescents than in adults (aOR=0.1; [CI] 95%: 0.0-0.7). Counseling and voluntary HIV testing are accepted in our labor rooms. Consistently offering this service in the labor room could be a catch-up strategy to be combined with antenatal care testing.


Thoracic irradiation in 3weeks for limited-stage small cell lung cancer: Is twice a day fractionation really needed?
Many Canadian institutions treat limited-disease small cell lung cancer with 40Gy in 15 fractions delivered once-a-day in 3weeks concomitantly with chemotherapy. This regimen is convenient and seems to be effective. Here, we report and compare with a literature review the outcomes of patients with limited-stage small cell lung cancer treated in our institution with this hypofractionated regimen. From January 2004 to December 2012, patients with limited-stage small cell lung cancer treated curatively with platinum-based chemotherapy and concurrent thoracic radiotherapy at a dose of 40Gy in 16 fractions once-a-day were eligible for this review. Sixty-eight patients fit the analysis criteria, including ten patients with small pleural effusion. The median age was 66years old. After a median follow-up of 77months for those alive, the median survival was 28months. At 3 and 5years respectively, the locoregional control rates were 67 and 64%, while the overall survival rates were 40 and 35%. Prophylaxis cranial irradiation was delivered to 68% of the patients. Grade 2 and 3 acute esophagitis occurred in respectively 49 and 9% of the patients. There was no grade 4 radiation-induced toxicity. All patients, except for one, completed their thoracic irradiation course without interruption. Once-a-day hypofractionated radiation with concurrent chemotherapy followed by prophylactic cranial irradiation is a practical regimen. Based on our experience and the published literature, it appears to be similarly effective as regimens using twice-daily fractionation in 3weeks, or once-daily in 6 to 7weeks with higher radiotherapy doses. Further prospective comparisons of hypofractionation with the current recommendations are needed.


A novel benzotriazole derivate with Twisted intramolecular charge transfer and Aggregation Induced emission features for proton determination.
Molecules with Aggregation-Induced Emission (AIE) effects could show strong emission in solid or aggregate form, thus they are suitable for applications in the field of solid luminescent materials. According to former reporting, AIE molecules are always J-aggregates. In this study, a new benzotriazole derivate with electron donor-acceptor structure was synthesized. (E)-4-(2-(1H-benzo[d] [1,2,3] triazol-1-yl) vinyl)-N, N-dimethylaniline (BTADA) has both TICT and AIE effect, even though it is H-aggregate. Furthermore, BTADA could respond to proton in solution and solid form. Due to its multiple binging sites, proton would bind to benzotriazole and dimethylaniline moiety successively when BTADA was exposed to acid, and the fluorescent color changed from green to yellow then blue as the concentration of proton increased. Such phenomena indicate BTADA has potential usage in proton detection.


Oncological Outcomes for Patients with European Association of Urology Very High-risk Non-muscle-Invasive Bladder Cancer Treated with Bacillus Calmette-Guérin or Early Radical Cystectomy.
European Urology Association (EAU) guidelines recommend immediate radical cystectomy (early RC) for patients with very high-risk (VHR) non-muscle invasive bladder cancer (NMIBC), with bacillus Calmette-Guérin (BCG) recommended only for those who refuse or are unfit for RC. To describe oncological outcomes following BCG or early RC in a contemporary cohort of patients with VHR NMIBC (EAU criteria). Patients diagnosed with VHR NMIBC between 2000 and 2020 were identified from our institutional NMIBC registry. The primary outcomes were overall survival (OS) and cancer-specific mortality (CSM). Secondary outcomes were the progression rate and high-grade recurrence (HGR) rate for patients receiving BCG. We identified 235 patients with VHR NMIBC, of whom 157 (67%) received BCG and 78 (33%) underwent early RC. The median follow-up was 52.8 mo. OS and CSM rates were 80.2% and 5.3% in the BCG group, and 88.1% and 4.9% in the early RC group, respectively with no significant difference in OS (p = 0.6) or CSM (p = 0.8) between the two groups. Among the patients treated with BCG, 5-yr HGR and progression rates were 41.9% and 17.4%, respectively; 39 patients (25%) underwent delayed RC after BCG. No significant difference in CSM emerged when comparing patients treated with delayed RC (after BCG) with those undergoing early RC (p = 0.86). Our findings suggest that intravesical BCG can be offered to patients as a resonable alternative to early RC for selected patients with VHR NMIBC. We evaluated outcomes for patients with very high-risk non-muscle-invasive bladder cancer (NMIBC) treated with BCG (bacillus Calmette-Guérin) versus early surgical removal of the bladder and found no differences in survival. We conclude that BCG could be offered to selected patients with this type of bladder cancer as a reasonable alternative to early bladder removal.


Inflammatory response to mental stress and mental stress induced myocardial ischemia.
Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. Patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90 min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarction patients. Of 607 patients analyzed in this study, (mean age 63 ± 9 years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p <0.0001), but not hsCRP. However, the changes in these markers were similar in those with and without MSIMI. Neither resting levels of these biomarkers, nor their changes with mental stress were significantly associated with MSIMI. Results in the replication sample were similar. Mental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90 min were significantly associated with MSIMI.


Inflammation in individuals with schizophrenia - Implications for neurocognition and daily function.
Individuals with schizophrenia display substantial deficits in neurocognition, resulting in poor daily functioning and disability. Recent reports have suggested that neurocognitive dysfunction in this population is linked to increased inflammation. However, there is paucity of evidence supporting this link, as well as lack of information about the putative link of inflammation to daily functioning. We examined neurocognition (MCCB) and daily functioning (SLOF), as well as inflammatory markers (TNF-α, IL-6, IL-1β, and IL-12p70) in 41 individuals with schizophrenia. Poor neurocognition was significantly associated with increased peripheral TNF-α and IL-12p70 (r = -0.44 and r = -0.38, respectively, controlling for BMI, depression and antipsychotic medication). Notably, difficulties with daily functioning were significantly associated with increased peripheral TNF-α (r = -0.51) and a trend with increased IL-12p70. Our findings support previous hypotheses linking neurocognitive impairment to increased inflammation in individuals with schizophrenia. Our results extend these associations in this population, linking inflammation to poor daily functioning in this population.


[Plasmoacanthoma. A contribution to the diagnosis, etiopathogenesis and nosology].
We report on a patient suffering from plasmoacanthoma which started from the right angle of the mouth and extended to the oral mucosa. The clinical tentative diagnosis of a malignant tumor was histologically supported by an immediate frozen section under surgery. Only histological examination of tumor material embedded in paraffin settled the diagnosis of plasmoacanthoma. On the base of mycological demonstration of Candida albicans on the tumor tissue, we discuss etiopathogenetic aspects of plasmoacanthoma as well as its nosologic position.


[Jaundice of the subcortical ganglia in a newborn caused by E. coli infection].
A case is reported of icterus of the subcortical ganglia in a premature newborn with total bilirubin level 7.42 mg%. The role of various risk factors in the aetiology of this icterus is discussed.


Drivers of Forest cover changes in and around Jorgo Wato Forest, West Wallagga, Oromia, Ethiopia.
Identifying the drivers of forest cover change is necessary information for planning sustainable use of natural resources. A study was conducted to identify the major drivers of forest covers changes in and around Jorgo Wato forest, West Wallagga Zone of Oromia National Regional State, Ethiopia. Purposive and random sampling selection of 120 household's interviews and 12 focus group discussions were used in this study. Agricultural expansion (especially coffee plantation), fuel wood extraction, wood for construction, logging (illegal), insecure tenure and use right, weak institutional performance, population growth and density were among the identified direct and indirect drivers of forest cover changes in the study area. Enhancing benefit sharing of the communities from forests/forest products is the main motivation for protection and sustainable management.


Closed Facebook groups and COVID-19: an evaluation of utilization prior to and during the pandemic.
Surgical education was limited during the COVID-19 pandemic due to redeployment, limited clinical activity, and cancelation of elective procedures and educational conferences. Closed Facebook groups became a tool for surgical education while upholding social distancing guidelines. We aim to evaluate the use of Online Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) closed Facebook groups, during and prior to the COVID-19 pandemic. Institutional Review Board evaluation and written consent was not indicated as the data does not pertain to any human subjects. Data files pertaining to new membership activity, posts, comments and reactions of eight closed Facebook groups. The pandemic group was defined as March 19th to April 30, 2020. The pre-pandemic group was defined as February 6th, to March 18th, 2020. The percentage increase of new memberships, posts, comments and reactions were calculated for each period. A two-tailed t-test, using a significance level of 0.05 was used to evaluate significance. A statistically significant increase in membership during the pandemic period was noted for each group. In regards to posts, the Flex Endo, Acute Care, Colorectal, Foregut, and Bariatric groups were noted to have a statistically significant increase in the pandemic period. Colorectal and Bariatric groups were the only two groups that were noted to have a significant increase in comments in the pandemic period. For reactions, Flex Endo, Colorectal, Foregut, and Bariatric groups were noted to have experienced a significant increase during the pandemic. The COVID-19 pandemic halted surgical education at all levels. The membership and utilization of closed Facebook groups increased significantly in many instances, demonstrating the importance of internet-based surgical education now and into the future. Further development of internet-based curriculums is warranted.


[Scanning electron microscopic examination of the shape and surface of enamel fissures prepared with the MSP air abrasion method of art-dent].
The specific structure of enamel fissures of molar teeth requires pre-treatment before a sealant can be effectively applied. The air abrasion technique is gaining acceptance for this purpose. This study was undertaken to examine the effect of air abrasion on the shape and surface of fissures at three levels (entry, middle part and fundus). Compressed air mixed with aluminum oxide particles resulted in enlargement of the fissure. Microretention sites in the form of pits and hollows were discovered at all levels studied.


Selection signatures and population dynamics of transposable elements in lima bean.
The domestication process in lima bean (Phaseolus lunatus L.) involves two independent events, within the Mesoamerican and Andean gene pools. This makes lima bean an excellent model to understand convergent evolution. The mechanisms of adaptation followed by Mesoamerican and Andean landraces are largely unknown. Genes related to these adaptations can be selected by identification of selective sweeps within gene pools. Previous genetic analyses in lima bean have relied on Single Nucleotide Polymorphism (SNP) loci, and have ignored transposable elements (TEs). Here we show the analysis of whole-genome sequencing data from 61 lima bean accessions to characterize a genomic variation database including TEs and SNPs, to associate selective sweeps with variable TEs and to predict candidate domestication genes. A small percentage of genes under selection are shared among gene pools, suggesting that domestication followed different genetic avenues in both gene pools. About 75% of TEs are located close to genes, which shows their potential to affect gene functions. The genetic structure inferred from variable TEs is consistent with that obtained from SNP markers, suggesting that TE dynamics can be related to the demographic history of wild and domesticated lima bean and its adaptive processes, in particular selection processes during domestication.


Transcriptome profiling in blood before and after hepatitis B vaccination shows significant differences in gene expression between responders and non-responders.
As the hepatitis B virus is widely spread and responsible for considerable morbidity and mortality, WHO recommends vaccination from infancy to reduce acute infection and chronic carriers. However, current subunit vaccines are not 100% efficacious and leave 5-10% of recipients unprotected. To evaluate immune responses after Engerix-B vaccination, we determined, using mRNA-sequencing, whole blood early gene expression signatures before, at day 3 and day 7 after the first dose and correlated this with the resulting antibody titer after two vaccine doses. Our results indicate that immune related genes are differentially expressed in responders mostly at day 3 and in non-responders mostly at day 7. The most remarkable difference between responders and non-responders were the differentially expressed genes before vaccination. The granulin precursor gene (GRN) was significantly downregulated in responders while upregulated in non-responders at day 0. Furthermore, absolute granulocytes numbers were significantly higher in non-responders at day 0. The non-responders already showed an activated state of the immune system before vaccination. Furthermore, after vaccination, they exhibited a delayed and partial immune response in comparison to the responders. Our data may indicate that the baseline and untriggered immune system can influence the response upon hepatitis B vaccination.


Region-Specific Disruption of Adenylate Cyclase Type 1 Gene Differentially Affects Somatosensorimotor Behaviors in Mice(1,2,3).
Cover FigureRegion-specific adenylyl cyclase 1 (AC1) loss of function differentially affects both patterning and sensorimotor behaviors in mice. AC1 is expressed at all levels of the somatosensory pathway and plays a major role in refinement and patterning of topographic sensory maps. Cortex-specific AC1 loss of function (CxAC1KO mice) does not affect barrel patterning and activation of specific barrels corresponding to stimulated whiskers and does not impair sensorimotor behaviors. While global (AC1KO) and thalamus-specific (ThAC1KO) AC1 loss of function leads to absence of barrel patterns, selective whisker stimulation activates topographically aligned cortical loci. Despite functional topography of the whisker-barrel cortex, sensorimotor and social behaviors are impaired, indicating the importance of patterning of topographical sensory maps in the neocortex. Adenylate cyclase type I (AC1) is primarily, and, abundantly, expressed in the brain. Intracellular calcium/calmodulin increases regulate AC1 in an activity-dependent manner. Upon stimulation, AC1 produces cAMP and it is involved in the patterning and the refinement of neural circuits. In mice, spontaneous mutations or targeted deletion of the Adcy1 gene, which encodes AC1, resulted in neuronal pattern formation defects. Neural modules in the primary somatosensory (SI) cortex, the barrels, which represent the topographic distribution of the whiskers on the snout, failed to form (Welker et al., 1996; Abdel-Majid et al., 1998). Cortex- or thalamus-specific Adcy1 deletions led to different cortical pattern phenotypes, with thalamus-specific disruption phenotype being more severe (Iwasato et al., 2008; Suzuki et al., 2013). Despite the absence of barrels in the "barrelless"/Adcy1 null mice, thalamocortical terminal bouton density and activation of cortical zones following whisker stimulation were roughly topographic (Abdel-Majid et al., 1998; Gheorghita et al., 2006). To what extent does patterning of the cortical somatosensory body map play a role in sensorimotor behaviors? In this study, we tested mice with global, cortical, or thalamic loss of AC1 function in a battery of sensorimotor and social behavior tests and compared them to mice with all of the whiskers clipped. Contrary to intuitive expectations that any region-specific or global disruption of the AC1 function would lead to similar behavioral phenotypes, we found significant differences in the degree of impairment between these strains.


Ca19.9 Positivity and Doubling Time Are Prognostic Factors of Mortality in Patients with Advanced Medullary Thyroid Cancer with No Evidence of Structural Disease Progression According to Response Evaluation Criteria in Solid Tumors.
Background: Serum Ca19.9 positivity is a prognostic factor for mortality in patients with advanced medullary thyroid cancer (aMTC), independently from calcitonin doubling time (DT). However, it is unknown whether aMTC patients who become positive for Ca19.9 also have progressive disease (PD) according to response evaluation criteria in solid tumors (RECIST) and whether Ca19.9 DT has a role in the management of aMTC patients. The aims of this study were to evaluate whether in aMTC, when serum Ca19.9 becomes positive, PD develops, and to determine the role of Ca19.9 DT in predicting mortality and PD. Patients and Methods: Serum Ca19.9 was periodically measured in 107 aMTC patients, and the DTs were calculated. Restaging of the disease was radiologically performed in 104 of 107 patients and PD was evaluated according to RECIST. Results: At the end of follow-up, 25 of 107 patients were Ca19.9 positive and PD was identified in 30 of 104 patients. No significant association was found between Ca19.9 positivity and PD, while there was a significant association between Ca19.9 positivity and mortality (p < 0.0001). Ca19.9 DTs <6 months and <1 year were not associated with PD but were associated with mortality (p < 0.0001 and p < 0.0001, respectively). In particular, 3 patients who had a Ca19.9 DT <6 months with no evidence of PD according to RECIST died of their disease after 6, 5, and 3 months, respectively. Conclusions: Serum Ca19.9 positivity and DTs <6 months and <1 year are prognostic factors for mortality but not for PD. Serum Ca19.9 positivity and DTs <6 months and <1 year should be considered in the decision-making process of whether to initiate systemic therapy even if there is no evidence of PD according to RECIST.


Detection and characterization of enteroviruses and parechoviruses in healthy people living in the South of Côte d'Ivoire.
Human enteroviruses (EVs) and parechoviruses (HPeVs) belong to the family Picornaviridae. Although most EV and HPeV infections remain asymptomatic, both pathogens can cause a wide spectrum of clinical manifestations ranging from respiratory or gastrointestinal symptoms to myocarditis, neonatal sepsis, and infections of the central nervous system. Aim of the present study was to investigate the spectrum of EVs and HPeVs in apparently healthy adults and children living in the South of Côte d'Ivoire. The study included 105 stool samples obtained from healthy individuals aged 0-53 years between June 2013 and December 2014 in the Sud-Como region of Côte d'Ivoire. After collection and shipment to Germany, the samples were analyzed by real-time PCR for the presence of EVs and HPeVs RNA. Molecular typing and virus isolation of all samples were performed.''é Out of 105 samples, 24 (22.8%) were EV positive and six (5.2%) were HPeV positive. Twenty-one EV positive samples could be characterized with serotypes belonging to EV group A-C, while three could not be further specified. Interestingly, several rarely described serotypes were identified, e.g., EV-C99, EV-B93, EV-C116, and EV-A119. Typing of HPeV positive samples resulted in HPeV-1 and -5 detections, while one isolate could not be assigned to the known HPeV types. This study showed a large variety of EV strains in healthy people in the South of Côte d'Ivoire and provided the first available data about HPeV infections in a sub-Saharan African country.


Epithelial ovarian cancer: a review of current management.
Epithelial ovarian cancer is the most lethal gynaecological cancer among women worldwide, with 6000 new cases diagnosed in the UK each year. Most women present with advanced disease, but, despite a good initial response to treatment, most relapse. The overall 5-year survival rate is 46%, although this drops to about 13% in women with advanced disease. Transvaginal ultrasound and the tumour marker CA125 are being investigated for screening in ongoing randomised trials. Treatment of ovarian cancer is dependent on clinical stage, and should always be managed within a multidisciplinary team. Most cases will require a pelvic clearance and adjuvant chemotherapy. Current guidelines by the National Institute of Clinical Excellence (NICE) recommend that first-line chemotherapy should include a platinum-based regimen with or without paclitaxel. Relapsed ovarian cancer is incurable; however, chemotherapy can improve quality of life and survival. Gene therapy, immunotherapy and signal transduction inhibitors are all potential future therapies, and are being investigated in ongoing clinical research. In this paper we review the literature on the epidemiology, pathology, clinical features and the current treatment options in epithelial ovarian cancer.


Fast quantitative determination of platinum in liquid samples by laser-induced breakdown spectroscopy.
The potential of laser-induced breakdown spectroscopy (LIBS) for the rapid determination of platinum in liquid silicone oils has been evaluated in the framework of on-line process control. A comparison of LIBS sensitivity between three setups designed for liquid analysis (static, liquid jet and flowing liquid) was performed using a 266 nm Nd/YAG laser irradiation. Best results were obtained using the flowing liquid setup and a similar limit of detection was obtained using the liquid jet. The effect of different buffer gases (Ar, He, N(2), etc.) on the signal sensitivity was studied in liquid jet analysis and best values were obtained with a nitrogen sheath gas. Detection limits were in the 100 mg/kg range for both setups. Quantitative determination of platinum in real liquid samples was also investigated using both liquid jet and flowing liquid setups. Calibration curves were plotted for Pt with the liquid jet and the flowing liquid setups under optimised temporal acquisition parameters (delay time and gate width). A normalisation using a silicon line was applied and recovery ranged from 3 to 15% for Pt in catalyst samples with both setups showing that LIBS is a sensitive and accurate method for on-line applications.


Solid lipid nanoparticles incorporated in dextran hydrogels: a new drug delivery system for oral formulations.
Solid lipid nanoparticles (SLN) containing or not (S)-(+)-2-(4-isobutylphenyl)propionic acid (ibuprofen) were prepared with Preciol ATO 5 as lipid phase by the hot homogenization technique and characterized through particle size analyses and zeta potential measurements. DSC experiments carried out on the freeze-dried samples of loaded SLN showed a shift of the melting endotherm of the lipid phase, with the maximum at a temperature value higher then that of the "empty" SLN. (1)H NMR of the nanosuspension allowed to calculate the encapsulation efficiency of the particles that was 52+/-3%. By adding dextran methacrylate (DEX-MA) to the aqueous phase and submitting the mixture to UV irradiation, systems of SLN (drug-loaded and unloaded) incorporated into a dextran hydrogel were prepared. Finally, dissolution studies of ibuprofen from the freeze-dried samples were performed. The comparison among the release profiles of ibuprofen from SLN, DEX-MA hydrogel and SLN/DEX-MA-hydrogel allows to affirm that this last system, retaining about 60% of the drug after 2h in acid medium and releasing it slowly in neutral solution, is suitable for modified delivery oral formulations.


A deoxyribonuclease of Diplococcus pneumoniae specific for methylated DNA.
A deoxyribonuclease specific for methylated DNA was isolated from Diplococcus pneumoniae. The enzyme, an endonuclease, degrades DNA for Escherichia coli to fragments of average molecular weight about half a million; it forms discrete fragments from phage lambda DNA. Methyl-deficient E. coli DNA is not attacked, neither is DNA from Micrococcus radiodurans, which contains no methylated adenine or cytosine. Nor is DNA from D. pneumoniae or phage T7 attacked. However, DNA from M. radiodurans, D. pneumoniae, and T7 is attacked after methylation with and E. coli extract. Methylated T7 DNA is degraded to discrete fragments. Although the genetic transforming activity of normal DNA from D. pneumoniae is not affected by the enzyme, transforming activity of methylated DNA is destroyed. The enzyme is designated endonuclease R Dpn I. Under certain conditions another enzyme of complementary specificity can be isolated. This enzyme, designated endonuclease R Dpn II, produces a similar pattern of fragments from the DNA of T7 without prior methylation of the DNA. It also degrades normal DNA for D. pneumoniae. It is suggested that this pair of enzymes plays a role in some unknown control process, which would involve a large fraction of the specific base sequences that are methylated in E. coli DNA and are present but not methylated in DNA from other sources.


Initial Study of the Extended STABILISE Technique for Complete Remodeling in Aortic Dissection.
Thoracic endovascular aortic repair (TEVAR) is the standard treatment for acute complicated type B aortic dissection (TBAD). However, long-term results reveal that TEVAR does not achieve a complete aortic remodeling and poses a risk of aneurysmal aortic degeneration. Distal re-entry treatment at the abdominal level seems to be necessary to obtain a complete remodeling in TBAD. Moreover, it is necessary to treat the aortoiliac bifurcation in patients with persistent true lumen collapse or limb ischemia. Between January 2018 and October 2019, 11 patients with acute or sub-acute complicated TBAD or non-A non-B aortic dissection were treated in our institution in an endovascular fashion. We performed the stent-assisted, balloon-induced intimal disruption and relamination in aortic dissection repair (STABILISE) technique in all cases, but 2 cases required complementary treatment of the aortoiliac bifurcation with a bifurcated AFX endograft system for limb ischemia due to true lumen collapse. Technical success was obtained in all patients. No procedural complications occurred. No postoperative deaths, stroke, paraplegia, mesenteric, or renal ischemia were observed, and no secondary intervention was necessary. Satisfactory aortic re-modeling was obtained after the follow-up periods with a 57.5% mean true lumen expansion. Our initial experience using the extended STABILISE (e-STABILISE) technique using a bifurcated AFX endograft did not result in any postoperative mortality or complications. Without additional data, this technique should be reserved for specific patients who require revascularization of the aortoiliac bifurcation.


The efficacy and safety of VEGF/VEGFR inhibitors in patients with recurrent or metastatic nasopharyngeal carcinoma: A meta-analysis.
Molecular targeted therapies against vascular endothelial growth factor (VEGF) receptor (VEGFR) have been explored in the treatment of recurrent or metastatic nasopharyngeal carcinoma (rmNPC). We conducted a meta-analysis to evaluate the efficacy and safety of VEGF/VEGFR inhibitors for treating rmNPC. Electronic databases were searched for eligible literature. Data on the objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), PFS rate, OS rate, and drug-related adverse events (AEs) were extracted. A total of 10 studies (published in 9 articles) that involved 357 patients were included. The pooled ORR was 37 % (95 % confidence interval [CI]: 17-60 %), the DCR was 70 % (95 % CI: 51-85 %), the mPFS was 5.69 months (95 % CI: 4.52-6.86), the mOS was 12.61 months (95 % CI: 10.23-14.99), the 1-year PFS rate was 34 % (95 % CI: 25-44 %), and the 1-year OS rate was 62 % (95 % CI: 38-83 %). The pooled incidence of grade 3/4 drug-related AEs was 27 %, while that of grade 5 AEs was 0.22 %. Further subgroup analysis showed that the pooled ORR and DCR for first-line VEGF inhibitors were 80 % (95 % CI: 74-86 %) and 94 % (CI: 82-100 %), respectively. Our meta-analysis is the first report to demonstrate the efficacy and safety of VEGF/VEGFR inhibitors in patients with rmNPC. Targeting VEGF/VEGFR therapy added to first-line chemotherapy achieved an excellent ORR and DCR, while the improvement in response rates did not translate to a prominent OS benefit.


The dual photopeak-area method applied to scintillation camera measurements of effective depth and activity of in vivo 123I-distributions.
Attenuation curves and photopeak ratios of 159 keV and 28 keV photons emitted in the decay of 123I have been studied using a scintillation camera equipped with an extra ADC for recording the pulse height distribution of the energy signal. Cavities of various sizes containing 123I-solution were placed at different depths in a water phantom in order to vary the effective depth i.e., the thickness of attenuating material above the cavity plus the distance to the centre of activity in the cavity. The centre of activity varies with the distribution of activity in the cavity, size of cavity, and the effective attenuation coefficient derived from the attenuation curves. From the photopeak ratio an average effective depth is determined which can be used for calculating the attenuation correction factor. The dual photopeak ratio has been used in clinical evaluation of thyoid 123I uptake measurements where effective depths ranging from 21 to 43 mm were obtained for the activity in the thyroid. Applications of the photopeak ratio method for renography with 123I-hippuran and blood flow studies using 133Xe or 127Xe and studies with many other radionuclides are also discussed.


Amelogenesis imperfecta in a Chinese family resulting from a FAM83H variation and the effect of FAM83H on the secretion of enamel matrix proteins.
To investigate the variant of an amelogenesis imperfecta (AI) family and to explore the function of the FAM83H (family with sequence similarity 83 member H) in the enamel formation. We investigated a five-generation Chinese family diagnosed with AI; clinical data was collected, whole-exome sequencing (WES) was conducted to explore the pathogenic gene and variants and Sanger sequencing was used to verify the variants. The three-dimensional protein structures of wild-type and mutant FAM83H were predicted using alpha fold 2. To study the possible regulatory function of Fam83h on amelogenesis, immunolocalization was performed to observe the expression of Fam83h protein in Sprague-Dawley rat postnatal incisors. The mRNA and protein level of amelogenin, enamelin, kallikrein-related peptidase-4 and ameloblastin were also detected after the Fam83h was knocked down by small interfering RNA (siRNA) in HAT-7 cells. A known nonsense variant (c.973 C > T) in exon 5 of FAM83H gene was found in this family, causing a truncated protein (p.R325X). Immunolocalization of Fam83h in Sprague-Dawley rat postnatal incisors showed that Fam83h protein expression was detected in presecretory and secretory stages. When Fam83h expression was reduced by siRNA, the expression of amelogenin, enamelin, kallikrein-related peptidase-4 decreased. However, the expression of ameloblastin increased. FAM83H gene variant (c.973 C > T) causes AI. FAM83H regulates the secretion of enamel matrix proteins and affects ameloblast differentiation. This study provided that FAM83H variants could influence enamel formation and provided new insights into the pathogenesis of AI.


Molecular characterization of a novel mitovirus from the plant‑pathogenic fungus Botryosphaeria dothidea.
Here, a novel mycovirus, Botryosphaeria dothidea mitovirus 1 (BdMV1), was isolated from a phytopathogenic fungus, Botryosphaeria dothidea, and its molecular characteristics were determined. BdMV1 has a genome of 2,667 nt that contains a single large open reading frame (ORF) using the fungal mitochondrial genetic code. The ORF encodes an RNA-dependent RNA polymerase (RdRp) of 727 amino acids with a molecular mass of 81.64 kDa. BLASTp analysis revealed that the RdRp domain of BdMV1 has 39.59% and 39.18% sequence identity to Plasmopara viticola associated mitovirus 43 and Setosphaeria turcica mitovirus 1, respectively. Phylogenetic analysis further suggested that BdMV1 is a new member of the genus Mitovirus within the family Mitoviridae. To the best of our knowledge, this is the first report of a mitovirus in B. dothidea.


Firing and contractile properties of human lower lip motor units during sustained isometric contractions.
Human subjects were taught to generate constant forces with their lips by contracting across a pair of hooks which held the corners of the mouth fixed in place. The force was measured with a strain gauge attached to one of the hooks. The activity of single motor units was recorded during production of small to near maximal levels of force. The recruitment and firing patterns of each unit were observed, and in vivo contractile properties of each unit were estimated using spike-triggered averaging of the high-gain force record. Recruitment of units was observed at all levels of force and recruitment level varied from trial to trial for each unit. Interspike interval variability was high at all levels of force. The twitch tensions of the units were all less than 10 g; the contraction times ranged from 16 to 90 ms. It is hypothesized that the differences between lip and limb motor unit properties in this task reflect the mechanical, anatomic, and neurophysiologic differences between these systems.


Multiple regulatory mechanisms for pH homeostasis in the gastric pathogen, Helicobacter pylori.
Acid-resistance in gastric pathogen Helicobacter pylori requires the coordination of four essential processes to regulate urease activity. Firstly, urease expression above a base level needs to be finely tuned at different ambient pH. Secondly, as nickel is needed to activate urease, nickel homeostasis needs to be maintained by proteins that import and export nickel ions, and sequester, store and release nickel when needed. Thirdly, urease accessary proteins that activate urease activity by nickel insertion need to be expressed. Finally, a reliable source of urea needs to be maintained by both intrinsic and extrinsic sources of urea. Two-component systems (arsRS and flgRS), as well as a nickel response regulator (NikR), sense the change in pH and act on a variety of genes to accomplish the function of acid resistance without causing cellular overalkalization and nickel toxicity. Nickel storage proteins also feature built-in switches to store nickel at neutral pH and release nickel at low pH. This review summarizes the current status of H. pylori research and highlights a number of hypotheses that need to be tested.


It's the End of the World and I Feel Fine: Soul Belief and Perceptions of End-of-the-World Scenarios.
Five studies tested the effects that soul beliefs have on reactions to end-of-the-world scenarios. In Studies 1 and 2, participants who firmly believe in an immortal soul showed less resistance to an article predicting the end of humanity than those without such belief. However, in Studies 3 to 5, thoughts of symbolic immortality made soul believers more resistant to scientific evidence predicting the end of humanity. These results suggest that belief in an immortal soul provides psychological protection against the threat of humanity's demise that does not hold for symbolic immortality beliefs.


Utilization and mechanism of action of tricyclic antidepressants in the treatment of chronic facial pain: a review of the literature.
Tricyclic antidepressants show promise in the treatment of chronic facial pain. The antinociceptive activity of this class of drugs appears to be independent of any antidepressant effects. An hypothesis is proposed that tricyclics antidepressants activate a descending serotonergic (5-HT1) antinociceptive pathway which in turn influences endogenous opioids. This antinociceptive pathway appears to utilize an endogenous pain modulation system. Future studies may demonstrate the operative mechanisms of action and open understanding as to etiologic factors.


Occurrence of hydrin 2 (vasotocinyl-Gly), a new hydroosmotic neurohypophyseal peptide, in secretory granules isolated from the frog (Rana esculenta) neurointermediate pituitary.
Neurohypophyseal secretory granules have been purified from the frog (Rana esculenta) neurointermediate pituitary gland by sucrose gradient centrifugation, and their polypeptide content has been analyzed by reverse-phase high-pressure liquid chromatography. Aside from vasotocin, mesotocin, and their associated neurophysins, hydrin 2 (vasotocinyl-Gly), previously identified in hydrochloric acid extracts, has been recognized. This finding supports the previous suggestion that hydrin 2, a peptide active on the water permeability of frog bladder and frog skin, is a secreted hormone involved in osmoregulation specific to amphibians. Hydrin 2 has not been found in neurosecretory granules of birds such as the goose.


Methods for Analyzing the Gut Microbiota in Diabetic Retinopathy.
The gut microbiome that inhabits human hosts plays an important role in the development of a healthy host immune system. Many studies have shown that gut microbiota is involved in the occurrence and development of diabetic retinopathy (DR). With the advent of sequencing technology of the bacterial 16S ribosomal RNA (rRNA) gene, microbiota studies are becoming more feasible. Here, we described a study protocol to characterize the microbiota composite in the DR and non-DR patients compared with healthy controls.


Molecular characterization and phylogeny of Anaplasma marginale, A. phagocytophilum and A. bovis in livestock of Bangladesh.
The emergence of Tick-borne Anaplasma spp. poses a significant threat to humans and animals worldwide. Traditional surveys based on examining blood smears overlook the existence of emerging pathogens. This study aimed to screen Anaplasma spp. in livestock species from diverse geographies with molecular tools. We collected 276 blood samples from cattle (Bos indicus), gayals (Bos frontalis) and goats (Capra hircus) in Jhenaidah, Bogura, Sirajganj and Bandarban districts, and Naikhongchari sub-district from June 2021 to March 2022. After that, a molecular screening was conducted through polymerase chain reaction (PCR) and sequencing was done to confirm the PCR results. The PCR assays were performed based on the analyses of groEL (Anaplasma marginale) and 16S rRNA (A. phagocytophilum and A. bovis). The Anaplasma spp. detected in this study were A. marginale (10.51%), A. phagocytophilum (0.72%), and A. bovis (63.77%). However, A. platys was not detected in this study. Among the screened pathogens, the detection of A. bovis (82.86%) was significantly high in the Bandarban district, while A. marginale was found only in cattle in this location. Regarding animal species, the occurrence of A. bovis was significantly higher in cattle. Moreover, the detection rate of A. marginale was significantly higher in adult cattle (≥2 years). The phylogenetic analyses revealed that the groEL sequences of A. marginale and 16S rRNA sequences of A. bovis and A. phagocytophilum were included in a single clade in the respective phylograms, showing a single genotype of each species circulating in Bangladesh. This study reports the existence of A. phagocytophilum in Bangladesh for the first time.


Correction: Improved Metabolic Models for E. coli and Mycoplasma genitalium from GlobalFit, an Algorithm That Simultaneously Matches Growth and Non-Growth Data Sets.
[This corrects the article DOI: 10.1371/journal.pcbi.1005036.].


Reconstitution of functionally efficient SecA-dependent protein-conducting channels: transformation of low-affinity SecA-liposome channels to high-affinity SecA-SecYEG-SecDF·YajC channels.
Previous work showed that SecA alone can promote protein translocation and ion-channel activity in liposomes, and that SecYEG increases efficiency as well as signal peptide specificity. We now report that SecDF·YajC further increases translocation and ion-channel activity. These activities of reconstituted SecA-SecYEG-SecDF·YajC-liposome are almost the same as those of native membranes, indicating the transformation of reconstituted functional high-affinity protein-conducting channels from the low-affinity SecA-channels.