Molecular and functional properties of protein SS1 from small ribosomal subunits of Streptomyces aureofaciens.
Small ribosomal subunits of gram-positive cells of Streptomyces aureofaciens contain an acidic protein designated SS1. Purified protein SS1 has the same mobility in sodium dodecyl sulfate/polyacrylamide gel as ribosomal protein S1 of Escherichia coli (apparent Mr 68 000). Protein SS1 was dissected under mild conditions with trypsin and generated fragments were compared with well-characterized fragments of protein S1. The protein SS1 contains a structure homologous with the C-terminal fragment of protein S1. The affinity of protein SS1 to poly(U) is virtually identical with that of E. coli protein S1. In contrast to protein S1, the addition of SS1 to partially S1-depleted ribosomes of E. coli had no stimulatory effect on poly(U)-directed synthesis of polyphenylalanine. At molar excess of SS1 over ribosomes, the protein had comparable inhibitory effect on polypeptide synthesis as had S1 of E. coli. Ribosomes of S. aureofaciens required about one order of magnitude higher concentration of poly(U) for maximum synthetic activity than did ribosomes of E. coli. The addition of proteins SS1 or S1 to ribosomes of S. aureofaciens had no stimulatory effect on translation of poly(U). Our data indicate that the high-molecular-mass acidic protein SS1 of small ribosomal subunits of S. aureofaciens exhibits only a part of the functional properties of E. coli protein S1.


Structure and regulation of Kit protein-tyrosine kinase--the stem cell factor receptor.
Signaling by stem cell factor and Kit, its receptor, play important roles in gametogenesis, hematopoiesis, mast cell development and function, and melanogenesis. Moreover, human and mouse embryonic stem cells express Kit transcripts. Stem cell factor exists as both a soluble and a membrane-bound glycoprotein while Kit is a glycoprotein receptor protein-tyrosine kinase. The complete absence of stem cell factor or Kit is lethal. Gain-of-function mutations of Kit are associated with several human neoplasms including acute myelogenous leukemia, gastrointestinal stromal tumors, mastocytomas, and nasal T-cell lymphomas. Binding of stem cell factor to Kit results in receptor dimerization and activation of protein kinase activity. The activated receptor becomes autophosphorylated at tyrosine residues that serve as docking sites for signal transduction molecules containing SH2 domains. Kit activates Akt, Src family kinases, phosphatidylinositol 3-kinase, phospholipase Cgamma, and Ras/mitogen-activated protein kinases. Kit exists in active and inactive conformations as determined by X-ray crystallography. Kit consists of an extracellular domain, a transmembrane segment, a juxtamembrane domain, and a protein kinase domain that contains an insert of about 80 amino acid residues. The juxtamembrane domain inhibits enzyme activity in cis by maintaining the control alphaC-helix and the activation loop in their inactive conformations. The juxtamembrane domain also inhibits receptor dimerization. STI-571, a clinically effective targeted protein-tyrosine kinase inhibitor, binds to an inactive conformation of Kit. The majority of human gastrointestinal stromal tumors have Kit gain-of-function mutations in the juxtamembrane domain, and most people with these tumors respond to STI-571. STI-571 binds to Kit and Bcr-Abl (the oncoprotein of chronic myelogenous leukemia) at their ATP-binding sites.


Use of an oxygen microsensor for the determination of intrinsic kinetic parameters of an immobilized oxygen reducing enzyme.
An oxygen microsensor was used to measure internal oxygen profiles in biocatalyst particles of different diameter and activity. The particles were made of agarose gel and contained an oxygen reducing enzyme, L-lactate mono-oxygenase. The kinetics of the enzyme could be well described by the Michaelis-Menten equation. From the internal substrate concentration profile the intrinsic kinetic parameters were determined by means of fitting a simulated profile to the measurements, using Marquardt's algorithm. The intrinsic kinetic parameters found following this procedure appeared to be independent of particle radius or enzyme loading used, proving the method to be reliable. These parameters were also compared with the kinetic parameters of the free enzyme which were determined in a biological oxygen monitoring system. The intrinsic kinetic parameters showed a decrease with a factor 2.3 for V(m) value and with a factor 2.7 for the K(m) value compared to the parameters for the free enzyme. From this the conclusion can be drawn that the immobilization as such or the carrier material not only can have an effect on the maximum intrinsic conversion rate (V(m)) but also on the affinity of the enzyme (K(m)) for oxygen.


A psychosocial pathway to paranoia: The interplay between social connectedness and self-esteem.
The quantity and quality of social contacts have been related to self-esteem, and both social relationships and self-esteem have been implicated in the pathways to paranoia. However, how social relationships interplay with self-esteem to trigger paranoia is not well understood. This study aims to investigate whether different measures of social connectedness (social support, loneliness, and desired friendship), as well as the frequency of social contact, impact paranoia and other positive and negative psychotic-like experiences (PLE) through the indirect effect of self-esteem. Data from a sample of 169 nonclinically ascertained participants oversampled for schizotypy scores were analyzed using two different approaches: retrospective trait-like and ecological momentary measures of social connectedness. Results showed that self-esteem mediates the pathways from poor social support and social longing, but not from loneliness, to paranoia and other cognitive PLE. In contrast, pathways from social connectedness to perceptual PLE and negative PLE were not mediated by self-esteem. Results were consistent across trait-like and momentary measures. Finally, self-esteem was not implicated in the pathways from the frequency of social contact and paranoia or other forms of PLE. These results provide a comprehensive picture of how social connectedness drives specific symptoms of psychosis through self-esteem. Findings underscore the need to explore separately the quality and quantity of social relationships and suggest that the subjective experience of meaningful social bonds is key social determinants of mental health. Therefore, addressing inadequacies of social connectedness could substantially improve symptomatic and functional outcomes of psychosis.


GLOBAL POPULATION STRUCTURE AND NATURAL HISTORY OF THE GREEN TURTLE (CHELONIA MYDAS) IN TERMS OF MATRIARCHAL PHYLOGENY.
To address aspects of the evolution and natural history of green turtles, we assayed mitochondrial (mt) DNA genotypes from 226 specimens representing 15 major rookeries around the world. Phylogenetic analyses of these data revealed (1) a comparatively low level of mtDNA variability and a slow mtDNA evolutionary rate (relative to estimates for many other vertebrates); (2) a fundamental phylogenetic split distinguishing all green turtles in the Atlantic-Mediterranean from those in the Indian-Pacific Oceans; (3) no evidence for matrilineal distinctiveness of a commonly recognized taxonomic form in the East Pacific (the black turtle C.m. agassizi or C. agassizi); (4) in opposition to published hypotheses, a recent origin for the Ascension Island rookery, and its close genetic relationship to a geographically proximate rookery in Brazil; and (5) a geographic population substructure within each ocean basin (typically involving fixed or nearly fixed genotypic differences between nesting populations) that suggests a strong propensity for natal homing by females. Overall, the global matriarchal phylogeny of Chelonia mydas appears to have been shaped by both geography (ocean basin separations) and behavior (natal homing on regional or rookery-specific scales). The shallow evolutionary population structure within ocean basins likely results from demographic turnover (extinction and colonization) of rookeries over time frames that are short by evolutionary standards but long by ecological standards.


Open-sourced semi-automatic program for ultrasound assessments of femoral trochlea cartilage health.
We developed an open-sourced program that accounts for the current limitations of B-mode ultrasound and extends the clinical utility of ultrasound for assessing femoral trochlear cartilage thickness. Images were collected on 18 patients with a history of knee surgery. By failing to account for ultrasound acoustics and beam refraction, cartilage thickness was underestimated by 26% and overestimated by 0-4%, respectively (p < 0.001). Comprehensive thickness measurements achieved by measuring the Euclidean distance between every point were significantly different than traditional single-location measurements or by using the area/length (p = 0.004-0.006). Sub-regions were significantly different than all whole regions of interest (p = 0.001-0.012).


[UPDATE ON CATARACT EXTRACTION SURGERY AND INTRA-OCULAR LENS IMPLANTATION].
Cataract extraction and intra-ocular lens (IOL) implantation is one of the most prevalent surgical interventions worldwide. In Israel more than 50,000 procedures were performed in 2013. The progress in cataract surgery is dual, including the surgical technique of the crystalline lens removal along with developments in IOL structure and optic characteristics. This review focuses on new techniques in cataract surgery and modern types of IOLs for implantation.


Crystal phase, shape and luminescence properties of LaPO4:Eu3+ nanocrystals.
We demonstrated the change of shape and crystal phase of LaPO4:Eu3+ nanomaterials by tuning the temperature of heating. The mechanism related to morphology control of LaPO4:Eu nanorods/nanoparticles are proposed and discussed. We describe the "oriented attachment" growth mechanism for nanorod-to-nanoparticles transformation with increasing the temperature of heating. It is found that the photoluminescence properties of LaPO4:Eu3+ nanostructures are sensitive to the crystal phase and shape. The drastic increase in luminescence intensity (12 times) and decay time increases from 2.66 to 3.34 ms with changing the shape (nanorod to nanoparticle) and crystal phase (hexagonal to monoclinic phase) for the samples prepared by emulsion based method. Our analysis suggests that the manipulation of the photoluminescence property can be done by changing the crystal phase of nanomaterials.


Enhancing hyaluronan pseudoplasticity via 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride-mediated conjugation with short alkyl moieties.
Hyaluronan (HA) is widely used in the clinical practice and in biomedical research. Through chemical modification, HA shear-thinning properties, essential for injectability and additive manufacturing, can be optimized. In this study, we employed 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) for grafting propylamine and butylamine to HA. A parametric study was performed to identify the optimal reaction conditions. Results showed that DMTMM amidation gives reproducible and accurate control over a range of degrees of substitution (DS) from 1% to 50% and proved reliable to tune viscoelasticity. At DS=3.0% for HA-propylamine and 3.7% for HA-butylamine a maximum for storage modulus and pseudoplasticity was found, whereas above or below this DS, rheological features go back to baseline values of pristine HA. Due to their singular rheological profiles, these derivatives are valuable biomaterials candidates for preparing bioinks and hydrogels for drug delivery and regenerative medicine.


HISTORICAL RESPONSE RATES OF SOMATOSTATIN ANALOGUES IN THE TREATMENT OF ACROMEGALY: A SYSTEMATIC REVIEW.
In a completed phase III study (C2305, Clinicaltrials.gov identifier: NCT00600886), the reported rate of biochemical control with octreotide long-acting release (LAR) was lower than rates historically reported in patients pretreated and/or selected for response with somatostatin analogue (SSA) therapy. To assess whether lower efficacy rates of octreotide LAR in C2305 were influenced by study design, a systematic review of the literature was performed to evaluate response rates in previously published studies in acromegaly with similar design characteristics. PubMed was used to search for English-language clinical studies of acromegaly published through May 2014. Prospective studies of medically naïve patients (≥20) treated with SSAs for ≤12 months that reported efficacy rates using composite endpoint measures (growth hormone [GH] and insulin-like growth factor 1 [IGF-1]) were included. Two separate authors independently screened abstracts and full-length articles of each study to determine eligibility. All authors met to review and reach consensus when primary reviewers disagreed on the inclusion or exclusion of specific studies. A total of 9 studies (N = 354 patients) were identified, with reported mean efficacy rates of 31% (range, 20-54%). Of note, reported mean efficacy rates were lower in studies enrolling patients naïve to any form of treatment (surgery, medical, and/or radiation) than in studies that enrolled only medically naïve patients. A limitation of this analysis was that inclusion criteria restricted the number of studies analyzed. Interpretation of biochemical response rates with SSAs is critically dependent on the context of the study and should be evaluated across clinical trials with similar study design characteristics.


Characterization using LC/MS of the absorption compounds and metabolites in rat plasma after oral administration of a single or mixed decoction of Shaoyao and Gancao.
Shaoyao-Gancao decoction (SGD), a traditional Chinese formulation containing Paeoniae Radix (SY) and Glycyrrhizae Radix (GC), is commonly used to relieve abdominal pain. However, the absorption and metabolites of the characteristic constituents of the two herbs in vivo have been reported rarely. The purpose of this study was to investigate the compatibility rationality and the mechanism of the enhanced efficiency of SGD. A single or a mixed decoction (SG and S+G, respectively) was orally administered to rats. Blood samples were collected at different intervals following treatment and analyzed by liquid LC/MS. A total of fifteen ingredients (denoted as M1 to M15) were found in both rat plasma after treatment with the two decoctions. Furthermore, the proposed structures of the remained twelve ingredients were obtained except M9, M10 and M15. The quality of the ingredients in the rat plasma showed no significant difference between the two decoctions. However, the quantity of twelve ingredients differed greatly, indicating that the absorption of SG was greater than that of S+G except M7, M12 and M15. As the compositions associated with the efficacy of SG and S+G were inconsistent, the degree of the absorption of the 15 ingredients by the gastrointestinal tract were different, which caused a significantly enhanced efficacy of certain ingredients. This study presents an exploration of the mechanism behind the improved efficacy of individual components in traditional Chinese medicine therapies through combination with other components.


Fatal haemophagocytic syndrome.
A fulminant clinical presentation with high fever and hepatosplenomegaly, together with a course of worsening pancytopenia, coagulopathy and liver failure, is suggestive of the haem syndrome (HPS). Bone marrow examination is diagnostic. We present 3 cases of HPS associated with different aetiologies including acute Ebstein Barr virus infection, T cell lymphoma, and malignant histiocytosis. In all the cases, the diagnosis was made late and the patients succumbed before definitive therapy could be administered.


High-efficiency mechanical energy storage and retrieval using interfaces in nanowires.
By molecular dynamics simulations, we demonstrate a new concept for mechanical energy storage and retrieval using surface energy as reservoir in body-centered cubic (bcc) tungsten nanowire, achieving a combination of unique features such as large and constant actuation stress (>3 GPa), exceptionally large actuation strain (>30%) and energy density, and >98% energy storage efficiency. The underlying mechanism is a shear-dominant diffusionless transformation akin to martensitic transformation, but driven by surface rather than bulk free energies, and enabled by motion of coherent twin boundary, whose migration has been shown to possess ultralow friction in bcc metals. Aside from energy storage, such surface-energy driven displacive transformations are important for phase transformation and energy-matter control at the nanoscale.


(Re)'Thinking' family in nursing care in pandemic times.
This study aimed to identify which strategies are being adopted to deal with family restrictions in health units and assess nurses' perceptions of including families in nursing care during the current pandemic. Due to the COVID-19 pandemic, health organisations limited access for visitors. Family centred care needs to be guaranteed, and alternatives for face-to-face interaction should be fostered. Therefore, there is an urgent need to rethink the family in nursing care during a pandemic. We conducted a descriptive exploratory mixed-method study in Portugal using an electronic questionnaire. The study included 192 nurses recruited using a non-probabilistic convenience sample. The study was reported using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. A total of 41.1% of participants (n = 79) reported that visits to their services were not authorised, and 66.7% (n = 128) reported resorting to video calls because of the restrictions imposed. Regarding attitude assessment, the average score of the scale was 77.9 (SD = 10.0), ranging between 26 and 98. When analysing the different dimensions of the 'Families' Importance in Nursing Care - Nurses Attitudes' scale, family data stand out as a burden. Although a large percentage of participants had a positive attitude towards families and tried to find strategies to maintain family centred care, many nurses still considered the family as a burden. The current COVID-19 pandemic may have aggravated this perception. IMPLICATIONS FOR NURSING PRACTICE, NURSING POLICY AND HEALTH POLICY: The continued implementation of family centred nursing practice is essential for child-well-being, including during the current pandemic. Therefore, having intervention policies with alternative forms of care is highly recommended.


Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations.
Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. The area under the receiver operating characteristic curve for diagnosing acute myocardial infarction was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays (P < .001). The area under the receiver operating characteristic curve of the combination of 2-hour absolute and relative change (hs-cTnT 0.98 [95% confidence interval {CI}, 0.97-0.99]; hs-cTnI, Beckman Coulter Inc, 0.97 [95% CI, 0.96-0.99]; hs-cTnI, Siemens, 0.96 [95% CI, 0.93-0.99]) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI assays. Reclassification analysis confirmed the superiority of absolute changes versus relative changes. Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infarction. The combination of absolute and relative changes provides a small added value for hs-cTnT, but not for hs-cTnI.


Confirmation of Echinococcus canadensis G8 and G10 in Idaho Gray Wolves ( Canis lupus) and Cervids.
We confirm the presence of Echinococcus canadensis genotypes G8 and G10 in gray wolves ( Canis lupus) and cervids in Idaho, US. Our results demonstrated that cystic echinococcosis remains a potential public health issue, indicating the need for regular deworming of domestic dogs, who often act as potential bridge hosts.


Recurrent pancreatitis as a manifestation of multisystem mitochondrial disorder.
In single cases mitochondrial disorders may manifest as pancreatitis, but recurrent, chronic pancreatitis with exacerbations of at least 15 times without morphological alterations of the pancreas but concomitant diabetes mellitus has not been reported. In a 57-year-old Caucasian male mitochondrial disorder was diagnosed at the age of 49 years upon epilepsy with generalized and focal seizures, cognitive decline, migraine, mitochondrial myopathy, polyneuropathy, diabetes mellitus, hypokalie-mia, hyperlipidemia, atrial fibrillation, heart failure, sicca syndrome, recurrent pancreatitis, chronic diarrhea, polydipsia, hyperhidrosis, steatosis hepatis, anemia, thrombopenia, an abnormal lactate stress test, and a muscle biopsy showing ragged-red muscle fibers, single completely COX-negative fibers, target fibers, increased number of sarcoplasmatic lipid droplets, but normal mitochondrial morphology on electron microscopy. Between the age of 33 years and the age of 44 years, at least 15 episodes of pancreatitis, manifesting as severe abdominal pain, and elevated exocrine pancreatic enzymes, but without morphological alterations of the pancreas, responding well to H2-blockers and food restriction had occurred. Recurrent pancreatitis without morphological alterations of the pancreas may be a feature of multisystem mitochondrial disorder resulting in diabetes mellitus. Physicians should familiarize with pancreatitis as a manifestation of a mitochondrial disorder and mitochondrial disorder should be excluded in patients with pancreatitis.


[Dirofilaria in the abdominal cavity].
Number of cases of filariasis have been recently reported in the Hungarian medical literature, most of them caused by Dirofilaria repens . Dirofilaria repens is a mosquito-transmitted filarioid worm in the subcutaneous tissue of dogs and cats. Human infection manifests as either subcutaneous nodules or lung parenchymal disease, which may even be asymptomatic. The authors report a human Dirofilaria repens infection of the abdominal cavity in a 61-year-old man,who underwent laparotomy for acute abdomen. Intraoperatively, local peritonitis was detected caused by a white nemathhelminth, measured 8 cm in size. Histocytology confirmed that the infection was caused by Dirofilaria repens.


Responses of testis, epididymis, and sperm of pubertal rats exposed to functionalized multiwalled carbon nanotubes.
The present study investigated the response of testes, epididymides and sperm in pubertal Wistar rats following exposure to 0, 0.25, 0.5, 0.75, and 1.0 mg kg(-1) functionalized multi-walled carbon nanotubes (f-MWCNTs) for 5 days. The results showed that administration of (f-MWCNTs) significantly increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner in both testes and sperm compared with control group. Moreover, the significant decrease in the activity of glutathione-S-transferase and glutathione level was accompanied with significant elevation in the levels of hydrogen peroxide and malondialdehyde in both testes and sperm of (f-MWCNTs)-treated rats. The spermiogram of (f-MWCNTs)-treated rats indicated significant decrease in epididymal sperm number, sperm progressive motility, testicular sperm number and daily sperm production with elevated sperm abnormalities when compared with the control. Exposure to (f-MWCNTs) decreased plasma testosterone level and produced marked morphological changes including decreased geminal epithelium, edema, congestion, reduced spermatogenic cells and focal areas of tubular degeneration in the testes. The lumen of the epididymides contained reduced sperm cells and there was mild to severe hyperplasia epithelial cells lining the duct of the epididymis. Collectively, pubertal exposure of male rats to (f-MWCNTs) elicited oxidative stress response resulting in marked testicular and epididymides dysfunction.


Challenges in the Interpretation of MRI Examinations Without Radiographic Correlation: Pearls and Pitfalls to Avoid.
As physics introduces more complex and seemingly thorough techniques to evaluate patient symptoms, cross-sectional imaging, especially magnetic resonance imaging (MRI), seems like the modality of choice to best help patients. However, musculoskeletal radiology (MSK) requires not just the excellent soft-tissue contrast provided by MRI but also an evaluation of the aggressiveness of a lesion, a detailed evaluation of osseous anatomy or distribution of disease, and a way to easily identify calcifications and gas in soft tissue in order to make the correct diagnosis. This article will demonstrate, through numerous cases, the importance of radiographs in the full characterization of MSK-related pathology. It will focus on imaging pearls and pitfalls to avoid when radiographs are not available and discuss the findings that can be expected if comparison radiographs were available.


Considerations for treating acne in ethnic skin.
Patients with ethnic skin are at an increased risk for developing postinflammatory hyperpigmentation (PIH) and keloid scarring subsequent to acne lesions. Treatment approaches for acne in darker skinned patients must balance early aggressive intervention with the selection of efficacious and nonirritating agents. Most patients with prominent or long-lasting PIH will require treatment with a topical retinoid and hydroquinone, the gold standard in the treatment of PIH. Keloids may be treated with surgical excision, but the rate of recurrence can be as high as 50%. Successful management of ethnic skin with acne can be achieved with the appropriate combination drug regimen and good patient compliance. For best results, clinicians should manage the entire grooming regimen of the skin and hair of their ethnic patients.


Elective Deliveries and the Risk of Autism.
Cesarean section and induced deliveries have increased substantially in the U.S., coinciding with increases in autism spectrum disorder. Studies have documented associations between cesarean section deliveries and autism spectrum disorder but have not comprehensively accounted for medical risks. This study evaluates the extent to which cesarean section and induced deliveries are associated with autism spectrum disorder in low-risk births. In this retrospective cohort study, California's birth records (1992-2012) were linked to hospital discharge records to identify low-risk births using a stringent algorithm based on Joint Commission guidelines. Autism spectrum disorder status was based on California Department of Developmental Service data. Logistic regression models were used to estimate associations between autism spectrum disorder and induced vaginal deliveries, cesarean section deliveries not following induction, and cesarean section deliveries following induction, with noninduced vaginal deliveries as the reference category. A total of 1,488,425 low-risk births took place in California from 1992 to 2012. The adjusted odds of autism spectrum disorder were 7% higher for induced vaginal deliveries (AOR=1.07, 95% CI=1.01, 1.14), 26% higher for cesarean section deliveries not following induction (AOR=1.26, 95% CI=1.19, 1.33), and 31% higher for cesarean section deliveries following induction (AOR=1.31, 95% CI=1.18, 1.45) than for noninduced vaginal deliveries. Lower gestational age and neonatal morbidities did not appear to be important underlying pathways. The associations were insensitive to alternative model specifications and across subpopulations. These results suggest that, in low-risk pregnancies, up to 10% of autism spectrum disorder cases are potentially preventable by avoiding cesarean section deliveries. After accounting for medical risks, elective deliveries-particularly cesarean section deliveries-were associated with a substantially increased risk of autism spectrum disorder.


BRADYKININOGEN, ANGIOTENSINOGEN AND KALLIDINOGEN.
The plasma globulins which produce the vasoactive polypeptides, bradykinin, kallidin and angiotensin, have been compared. After incubation of plasma with kallikrein and exhaustion of its kallidinogen, subsequent incubation with trypsin did not result in formation of bradykinin, showing that bradykininogen had also been exhausted and suggesting that kallikrein and trypsin use the same substrate. Kallidin and bradykinin formation was not prevented by acid-treatment of plasma, though heat-denatured substrate produced kallidin less readily. Kallikrein could exhaust plasma bradykininogen without affecting levels of angiotensinogen. Following nephrectomy of dogs, plasma angiotensinogen levels rose whereas bradykininogen levels did not. These results confirm the belief that bradykininogen differs from angiotensinogen but not from kallidinogen.


Diagnosis of early gastric cancer seen as less malignant endoscopically.
In order to make the endoscopic diagnosis of early gastric cancer more accurate, we determined the endoscopic and clinicopathological characteristics of the 129 cases of early gastric cancer with less malignant appearance among the 978 cases of the disease with a solitary lesion detected at the National Cancer Center Hospital during the period between 1962 and 1981. According to findings required to make a differential diagnosis, the endoscopic appearance of the 978 cases were divided into the following four groups: 170 cases of polypoid, 587 of ulcerative, 119 of gastritis-like and 102 of advanced cancer-like. Among the four groups, the frequency of cases with less malignant appearance was quite high in the gastritis-like group. The lesion in this group was defined as the cancerous lesion which shows only superficial mucosal abnormality, not associated with any polypoid or ulcerative components. Chronologically, it has been rapidly increasing in recent years. These two paradoxical phenomena in the gastritis-like group, that is, "high frequency of less malignant appearance" and "increase in number of cases" not only indicate the inadequacy of the conventional criteria for the recent cases but also show that the gastritis-like malignancy is detectable. New additional endoscopic criteria for the gastritis-like malignancy, for example, irregular margin of the shallow mucosal depression, disproportion of the mucosal granularity, irregularity on the erythematous change and discoloration are essential in order to detect much more cases with less malignant appearance.


Mapping the fluorophilicity of a hydrophobic pocket: synthesis and biological evaluation of tricyclic thrombin inhibitors directing fluorinated alkyl groups into the p pocket.
In the completion of our fluorine scan of tricyclic inhibitors to map the fluorophilicity/fluorophobicity of the thrombin active site, a series of 11 new ligands featuring alkyl, alkenyl, and fluoroalkyl groups was prepared to explore fluorine effects on binding into the hydrophobic proximal (P) pocket, lined by Tyr 60A and Trp 60D, His 57, and Leu 99. The synthesis of the tricyclic scaffolds was based on the 1,3-dipolar cycloaddition of azomethine ylides, derived from L-proline and 4-bromobenzaldehyde, with N-(4-fluorobenzyl)maleimide. Introduction of alkyl, alkenyl, and partially fluorinated alkyl residues was achieved upon substitution of a sulfonyl group by mixed Mg/Zn organometallics followed by oxidation/deoxyfluorination, as well as oxidation/reduction/deoxyfluorination sequences. In contrast, the incorporation of perfluoroalkyl groups required a stereoselective nucleophilic addition reaction at the "upper" carbonyl group of the tricycles, thereby yielding scaffolds with an additional OH, F, or OMe group, respectively. All newly prepared inhibitors showed potent biological activity, with inhibitory constants (K(i) values) in the range of 0.008-0.163 microM. The X-ray crystal structure of a protein-ligand complex revealed the exact positioning of a difluoromethyl substituent in the tight P pocket. Fluorophilic characteristics are attributed to this hydrophobic pocket, although the potency of the inhibitors was found to be modulated by steric rather than electronic factors.


Knowledge and Perception Toward Neuromodulation Devices Among Medical Students at Umm Al-Qura University.
Introduction Neurologic and psychiatric disorders affect many people worldwide and are crucial to medical care. It is crucial to note that primary care doctors initially evaluate patients who will eventually require neuromodulation (NM) therapy. There is a growing concern about the extent of medical students' knowledge regarding NM therapy. Insufficient education and limited exposure of future doctors to different treatment approaches can limit their ability to refer patients promptly and appropriately, thereby impeding access to necessary treatment. Methods The study employed a non-probability stratified snowball sampling technique to recruit participants. The population consisted of undergraduate medical students (excluding interns) at Umm Al-Qura University (UQU) in Saudi Arabia. Data collection was conducted through an online questionnaire. Results The sample comprised 301 medical students, with an average age of 21.62±1.54 years (ranging from 18 to 25). The majority were female (65.1%), and in the clinical years (57.8%), a considerable portion of respondents (57.5%) lacked awareness that NM devices are approved by the FDA for treatment. Both pre-clinical and clinical-year students exhibited insufficient knowledge (91.3% and 91.4%, respectively). Females showed a higher proportion (95.9%) of poor attitudes toward NM compared to males (83.8%). Notably, preclinical students showed a higher level of knowledge (11.0%) compared to clinical students (6.3%). Conclusions The study revealed a significant lack of knowledge among medical students regarding NM devices. This is concerning given the growing prevalence of NM devices in clinical practice. To ensure optimal patient care, it is crucial to provide comprehensive education on NM devices to medical students.


Characteristics of male spouse abusers consistent with personality disorders.
Researchers and clinicians have tended to minimize the role of psychological characteristics of male spouse abusers, which has restricted the selection of potentially appropriate treatment interventions. A review of clinical literature on psychological characteristics of male batterers, including some studies incorporating psychometric testing, suggests that many of the characteristics of batterers are consistent with DSM-III criteria for personality disorders. Several authors have defined subtypes of batterers, which can be associated with specific types of personality disorders. Treatment programs for male spouse abusers should address the specific problems presented by patients with personality disorders, including alcohol-abusing batterers, a particularly difficult group to treat.


Violence among street-involved youth: the role of methamphetamine.
This study investigated a possible association between violence and the use of drugs, particularly methamphetamine and alcohol. Cross-sectional, baseline data were derived from the At-Risk Youth Study, a prospective cohort of street-involved youth in Vancouver, Canada. Subjects were asked whether they had suffered or perpetrated violence in the 6 months prior to the interview. In total, 478 youth were enrolled, with a median age of 22 years (interquartile range = 20.0-23.9); 230 (48%) reported having been victims of violence, while 165 (34.5%) reported having perpetrated violence. Daily methamphetamine use was not associated with either outcome. In a multivariate analysis, daily alcohol consumption was significantly associated with being a victim (adjusted odds ratio = 2.10) and a perpetrator (adjusted odds ratio = 2.02) of violence. A history of abuse, failing a grade, and dealing drugs were also independently associated with violence, while having a regular partner was protective. Contrary to popular media reports that methamphetamine causes violence, we found no association. The association of alcohol with violence, though, has implications for screening and intervention programs.


Rapid point-of-care detection of SARS-CoV-2 infection in exhaled breath using ion mobility spectrometry: a pilot study.
An effective testing strategy is essential for pandemic control of the novel Coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Breath gas analysis can expand the available toolbox for diagnostic tests by using a rapid, cost-beneficial, high-throughput point-of-care test. We conducted a bi-center clinical pilot study in Germany to evaluate breath gas analysis using multi-capillary column ion mobility spectrometry (MCC-IMS) to detect SARS-CoV-2 infection. Between September 23, 2020, and June 11, 2021, breath gas measurements were performed on 380 patients (SARS-CoV-2 real-time polymerase chain reaction (PCR) positive: 186; PCR negative: 194) presenting to the emergency department (ED) with respiratory symptoms. Breath gas analysis using MCC-IMS identified 110 peaks; 54 showed statistically significant differences in peak intensity between the SARS-CoV-2 PCR-negative and PCR-positive groups. A decision tree analysis classification resulted in a sensitivity of 83% and specificity of 86%, but limited robustness to dataset changes. Modest values for the sensitivity (74%) and specificity (52%) were obtained using linear discriminant analysis. A systematic search for peaks led to a sensitivity of 77% and specificity of 67%; however, validation by transferability to other data is questionable. Despite identifying several peaks by MCC-IMS with significant differences in peak intensity between PCR-negative and PCR-positive samples, finding a classification system that allows reliable differentiation between the two groups proved to be difficult. However, with some modifications to the setup, breath gas analysis using MCC-IMS may be a useful diagnostic toolbox for SARS-CoV-2 infection. This study was registered at ClinicalTrials.gov on September 21, 2020 (NCT04556318; Study-ID: HC-N-H-2004).


Gleason grading of prostate cancer in needle core biopsies: a comparison of general and urologic pathologists.
The Gleason grading of prostate carcinoma (PCa) in needle core biopsies is a major determinant used in management planning. The objective of this study was to evaluate the concordance between general pathologists Gleason grading and that of a urologic pathologist in our community. Retrospective review conducted at three tertiary care hospitals in Jeddah and Riyadh for all prostatic biopsies with carcinoma from January 2002 to January 2011. Gleason scores assigned by the original pathologist were compared with that of the reviewing urologic pathologists. Biopsies were originally obtained and diagnosed at different referring hospitals and independent laboratories. The kappa test was used to evaluate agreement between the original and review scores. For 212 biopsies the exact concordance of the Gleason score assigned by the original pathologist and the reviewer was 38.7% (82/212). However, when grouped into the main four-score categories of 2-4, 5-6, 7, and 8 or greater, disagreement was noted in 88 (41.5%) biopsies; 87 were upgraded and 1 was downgraded on review. When grouped into two-score categories of low grade (≤6) and high grade (≥7), disagreement was noted in 32 (15%) of the biopsies. Gleason grade score shows that there was only slight to fair agreement between outside and review scoring (kappa=0.43). When using only low versus high grade categorization, there was good agreement (kappa=0.69). Almost all of the cases with score disagreement were upgraded on review.


Comparative analysis of the blood flow values of patients with type 2 diabetes mellitus presenting with chronic periodontitis, patients with chronic periodontitis only and healthy individuals.
Laser Doppler flowmetry (LDF) is a non-invasive technique used for various reasons in medicine and dentistry. There are many reports of vascular and microcirculatory changes in patients with diabetes mellitus. The aim of the study was to assess the gingival blood flow (GBF) measurements in patients with chronic periodontitis (Group 1), patients with chronic periodontitis and Type 2 diabetes mellitus (Group 2) and healthy controls (Group 3). Forty-eight individuals were included in the study and divided into three groups. Gingival blood flow measurements were taken from 16 points in the upper vestibular aspect of six anterior teeth using LDF probe. In addition, plaque index (PI), gingival index (GI), probing depth (PD) and attachment loss (AL) were registered to determine the periodontal status. Results showed a significant correlation (p < 0.05) in clinical indices and GBF among the groups. Moreover, in Group 1, there was a correlation between GI and AL and between PD and AL. In Group 2, a correlation was observed between PI and AL and between GI and GBF. The results revealed an increase in GBF value in the chronic periodontitis group with Type 2 diabetes mellitus compared with the group with chronic periodontitis only. Diabetes can also affect GBF due to the nature of the disease, which affects the microcirculatory status.


Three-Dimensional Printing of a Transconjunctival Vitrectomy Trocar-Cannula System.
The aim of this paper was to study the feasibility of manufacturing a customizable trocar-cannula system for vitreoretinal surgery utilizing commercially available three-dimensional (3D) printing technology. A digital model of a trocar-cannula system for vitreoretinal surgery was created using computer-aided design (CAD) software and printed utilizing a laser-sintering 3D printer in modified ABS thermoplastic material. The trocar-cannula prototypes were tested in pig eyes. A customizable digital model was created using commercially available CAD software. Three trocar-cannulas were printed. The smallest cannulas that could be printed had dimensions between 21 and 22G. The trocar-cannulas were inserted in pig eyes after performing sclerotomies with a commercially available 20G MVR blade. One cannula broke during insertion. This study demonstrates the feasibility of printing a transconjunctival vitrectomy trocar-cannula system with commercially available 3D print technology. The 3D printer and build material used resulted in trocar-cannulas with functional limitations including a minimum size achievable and mechanical resistance.


Transplantation of isolated hepatocytes into the pancreas.
In previous research into hepatocyte transplantation (HTX) the spleen was the preferred acceptor organ for isolated donor hepatocytes. In this study the pancreas was tested as an acceptor organ for HTX. HTX into the pancreas or spleen was performed by injection of 10(7) isolated hepatocytes into the parenchyma of these organs. Intrapancreatic hepatocytes showed good viability 3 months after syngenic HTX as assessed by histological and immunocytochemical parameters. Definite proof of sustained metabolic activity of normal hepatocytes, 3 months after transplantation into the pancreas of congenitally jaundiced rats, was obtained by demonstration of bilirubin conjugates in bile of the recipients: 4.0% of total biliary bilirubin was conjugated. Intrasplenic HTX, however, was more effective and resulted in a conjugated fraction of 17.7% of total biliary bilirubin (p less than 0.001). Reduction of total plasma bilirubin was significant with both methods, but more pronounced in intra-splenic HTX. Bile drainage from the hepatocellular transplant via the pancreatic excretory system into the gut was not observed: conjugated bilirubins were not found in pancreatic juice of HTX-treated jaundiced rats. Intrapancreatic HTX did not adversely affect the host rat; evidence of pancreatitis or diabetes was not found. It is concluded that the pancreas is a suitable acceptor organ for HTX. However, intrapancreatic HTX appears to be less effective than intrasplenic HTX in the treatment of enzyme deficiency disease.


Understanding the relationship between Plasmodium falciparum growth rate and multiplicity of infection.
Natural infections with Plasmodium falciparum are often composed of multiple concurrent genetically distinct parasite clones. Such multiclonal infections are more common in areas of high transmission, and the frequency of multiclonal infection also varies with age. A number of studies have suggested that multiclonal infection predicts the risk of subsequent clinical malaria. The multiplicity of infection is determined by the rate of new infections, the number of clones inoculated at each mosquito bite, and the duration of infections. Here, we used a mathematical modeling approach to understand how variation in the growth rate of blood-stage parasites affects the observed multiplicity of infection (MOI), as well as the relationship between the MOI and the risk of subsequent malaria. We then analyzed data from a study of multiclonal infection and malaria in an malaria-endemic area in Tanzania and show that the proportion of multiclonal infections varies with age and that the observed relationship between multiclonal infection and subsequent clinical events can be explained by a reduction in blood-stage parasite growth with age in this population.


A study on the quality of study skills of newly-admitted students of Fasa University of Medical Sciences.
Some students attribute their academic failure to such factors as low aptitude, unavailability of resources, and bad luck. However, we can dare to say that the most important factor playing a role in academic success is students' little acquaintance with learning and study skills. This study aimed at examining the quality of study skills in newly-admitted students of Fasa Medical University so that the results can be used in holding teaching courses in study skills. The present study is a cross-sectional descriptive study. The sampling was done of all the newly-admitted students in the first semester of 2012 academic year including 94 students of Medicine, Nursing and Laboratory Technology. The data were collected through a questionnaire, consisting of two parts. The first part included items on demographic information of the subjects (such as sex, field of study, number of hours dedicated to studying, student's rank in Konkour, and the National University entrance exam. The second part was composed of 19 special items on such domains as 'Time management', 'Concentration', 'Class note-taking', 'Studying' and 'Taking exams' with 4, 5, 4, 3, 3 items, respectively. The checklists were filled in using Likert Scale. The collected data was then analyzed using an SPSS 14, through which descriptive statistics as mean, standard deviation and multiple regressions were obtained. Moreover, the data were analyzed using Independent Sample t and ANOVA tests. The results showed that the range of the students' study skills was 2.35, being rather below the normal level; the highest mean belonged to 'concentration' (2.56), but the lowest mean was that of 'time management' (2.05).Through ANOVA test, it was also shown that there was no significant difference between the students of Medicine, Nursing and Laboratory Sciences regarding their scores on 'study skills' as (p=0.646). In addition, through independent sample t-test, it was shown that there was no significant difference between the subjects' 'sex' and 'study skills' as the p-value was 0.584. On the other hand, through multiple regressions, the results indicated that there was a significant difference between 'taking exams' and 'studying' (p=0.003), between 'class note-taking' and ''taking exams' (p=0.004), between 'concentration' and ''taking exams' (p=0.002), and between 'time management' and 'taking exams' (p=0.001). Regarding the very important role of study skills in learning, it is recommended that 'study skills' and 'study habits' courses be included in the students' curriculum formally or implemented as workshops for students.


Survey of the dental health and denture status of institutionalized elderly patients in Ireland.
An investigation was conducted to establish the dental status of 368 elderly patients in two geriatric hospitals in Limerick, Ireland, in terms of denture status and the number of teeth present. Seventy eight percent of those examined were edentulous, but only 27% of edentulous patients were wearing maxillary and mandibular dentures. A further 18% wore a maxillary denture only, 21% had dentures made but no longer wore them, and 33% had never had dentures. Forty-four patients had some maxillary and mandibular teeth present and 20 of these had sufficient teeth for masticatory purposes. Very few patients, edentulous or dentate, complained of any problems, although 27 were felt to require extraction of one or more teeth.


[Transabdominal choriocentesis for rapid prenatal diagnosis in the 2d trimester: experiences in 147 pregnant patients].
The simple technique of ultrasound guided transabdominal choriocentesis allows rapid karyotyping early in the second trimester. Choriocentesis was carried out in 147 pregnancies at (genetic) risk during the 13th-19th week of gestation. Results of reliable karyotyping were available within 2-4 days. In 146 (99.3%) women a sufficient amount of chorionic villi could be collected with maximal two needle insertions. An abnormal karyotype was found in four pregnancies, which were terminated selectively on parental request. In all pregnancies a follow-up by ultrasound was performed 4 weeks after the procedure, one (0.7%) unexplained fetal death occurred, 143 pregnancies remained uneventful. We concluded that transabdominal choriocentesis is a simple rapid and relatively safe method, which can be useful for rapid karyotyping during the second trimester.


[Giant sacral schwannoma with pelvic extension. Therapeutic strategy. Apropos of a case].
A 48-year-old woman was admitted for acute urinary retention. Clinical pelvic examination disclosed a voluminous retro-rectal mass. Plain X-rays, pelvic echography, computerized tomography and MRI were all consistent demonstrating the presence of a 15cm-diameter lesion in the pelvic space with sacral erosion at S3-S4 and extension in the sacral canal up to S2. After a preoperative embolization, the tumor was removed in a two-stage procedure. First, an anterior transabdominal approach dissected the superior and lateral aspects of the tumor. To make easier the intra-abdominal dissection and to avoid any rectosigmoid necrosis, hysterectomy and rectosigmoid section with an end-colostomy were performed. Lastly, a piecemeal removal of the whole tumor was achieved using a posterior approach. At 6 months postoperatively, she recovered a satisfactory urinary control and the colo-rectal anastomosis was then successfully performed. Clinically only a slight hypesthesia of the left perineum was present. In the recent literature, 21 cases were described with similar clinical presentation and similar technical problems to achieve a complete treatment. In the discussion, details of the surgical anterior and posterior approaches are given. Before deciding the most appropriate surgical approach for such a mass, a biopsy is useful to determine whether total removal is relevant. A preoperative embolization can help to reduce the duration of the procedure and the loss of blood.


Ultrastructural pathology of pediatric myocardium in acute ischemia: bioptic study before and after treatment with cardioplegic solution.
Protecting the myocardium from the risk of acute ischemia during heart surgery is still an unsolved problem; the problem is even more open and more pressing in pediatric heart surgery. To meet this greater risk it is advisable to use a cardioplegic solution with a composition that is better suited to the particular morphofunctional conditions of the myocardium in the child, i.e., a solution offering greater protection. To this purpose the authors experimented with Celsior cardioplegic solution during heart surgery in children to evaluate the efficacy compared to the standard St. Thomas solution. In this comparative study 15 children were treated with Celsior cardioplegic solution and 15 others with St. Thomas cardioplegic solution. Each patient underwent 2 biopsies of the myocardium, the first before cardioplegic treatment and the second immediately after reperfusion. In both groups, focal lesions involving both the cardiomyocytes and the vascular-stromal structures were randomly found. The former had undergone a necrotic-regressive process with changes in the myofibrils and the mitochondria. The vascular-stromal structures showed changes in the permeability of the capillary endothelia, with interstitial edema. The results show the lesions to be similar in the 2 groups both on a quality and quantitative level.


[Lectins in Viscum:a progress review].
Viscum plants,the evergreen perennial parasitic shrubs or subshrubs,are mainly distributed in tropical and subtropical regions. There are about 70 Viscum species around the world,including 11 species and one variety in China. Mistletoe lectins are typeⅡ ribosome-inactivating proteins( RIPs) extracted from Viscum plants with anticancer and immunoregulatory activities. Many studies have focused on the mistletoe lectins isolated from V. album in Europe and V. album var. coloratum distributed in South Korea,respectively,and several preparations,such as Iscucin Ⓡ,were developed and clinically applied for cancer treatment. Although Viscum plants are widely distributed in China,only a few studies of mistletoe lectins have been reported. The recent progress of mistletoe lectins was reviewed from extraction,purification,quantitative/qualitative detection,molecular structure,pharmacological activities,toxicities,and clinical application,aiming at providing a reference for in-depth research and utilization of mistletoe lectins produced in China.


Selective hair therapy: bringing science to the fiction.
Investigations on carrier-based drug delivery systems for higher selectivity in hair therapy have clearly evolved from dye release and model studies to highly sophisticated approaches, many of which specifically tackle hair indications and the delivery of hair-relevant molecules. Here, we group recent hair disease-oriented work into efforts towards (i) improved delivery of conventional drugs, (ii) delivery of novel drug classes, for example biomolecules and (iii) targeted delivery on the cellular/molecular level. Considering the solid foundation of experimental work, it does not take a large step outside the current box of thinking to follow the idea of using large carriers (>500 nm, unlikely to penetrate as a whole) for follicular penetration, retention and protection of sensitive compounds. Yet, reports on particles <200 nm being internalized by keratinocytes and dendritic cells at sites of barrier disruption (e.g., hair follicles) combined with recent advances in nanodermatology add interesting new facets to the possibilities carrier technologies could offer, for example, unprecedented levels of selectivity. The authors provide thought-provoking ideas on how smart delivery technologies and advances in our molecular understanding of hair pathophysiology could result in a whole new era of hair therapeutics. As the field still largely remains in preclinical investigation, determined efforts towards production of medical grade material and truly translational work are needed to demonstrate surplus value of carrier systems for clinical applications.


Pulse transit time as a measure of inspiratory effort in children.
The current criterion standard for measuring inspiratory effort, esophageal manometry, is an invasive procedure that young patients find intolerable. Inspiratory effort can also be assessed noninvasively by measuring the pulse transit time (PTT). PTT is the time the pulse wave (PW) takes to travel between two arterial sites (normally heart to finger). The speed at which the PW travels is directly proportional to arterial BP. When BP rises, PTT shortens. Conversely, when BP falls, PTT lengthens. In this study, we investigated PTT as a measure for evaluating inspiratory effort in children. We studied 15 healthy children (age range, 5 to 12 years; mean age [+/- SD], 8.3 +/- 2.74; 9 male children) selected from patients referred to our pediatric center for routine assessment. We assessed changes in the PTT during breathing against known resistances in awake children. Resistance was applied to the nose and mouth with a modified, two-way, nonrebreathing facemask. Our data show a good correlation between the induced inspiratory effort and the amplitude of PTT variations. PTT should be a useful method for quantifying changes in inspiratory effort due to augmented upper airway resistance in awake children.


Pubic Symphysis Separation and Regression in Vaginal versus Cesarean Delivery.
To quantify the association of pubic symphysis separation with mode of delivery and follow the resolution of this physiologic separation in the postpartum period. Prospective observational cohort study that recruited two cohorts of primiparous women: those undergoing vaginal and cesarean delivery (45 and 46 patients, respectively). Chart review collected intrapartum factors. Patients were followed with serial anterior-posterior radiographs within 48 hours of delivery and at 6, 12, and 24 weeks postpartum, to evaluate the extent of pubic symphysis separation. Differences between the two cohorts in intrapartum factors were assesses as was pubic symphysis separation at each time point. Mean age of women was 25.8 (SD 5.1) years, and 56% were White. Mean birth weight was 3.5 (SD 0.52) kg. Mean immediate postpartum pubic symphysis separation was 7.6 (SD 2.2) mm and did not differ between groups, at 7.18 mm for vaginal delivery versus 8.04 mm for cesarean delivery (CD; P = 0.08). Pubic symphysis separation was not significantly different for CD with and without labour. Black race and obesity were associated with increased pubic symphysis separation. No intrapartum events were related to extent of separation. Normalization of pregnancy pubic symphysis separation to 4-5 mm occurred by 6 weeks postpartum. Separation of >10mm and <15mm occurred in 10 of the 91 women and occurred after vaginal and cesarean delivery. The widest pubic symphysis separation was observed in 3 patients after vaginal delivery. Physiological pubic symphysis separation occursduring pregnancy and regresses postpartum with minimal effects from labour and delivery. Cesarean deliverydoes not prevent physiological pubic symphysis separation.


Tissue lesions of tiger salamanders (Ambystoma tigrinum): relationship to sewage effluents.
A population of facultative neotenous tiger salamanders (A. tigrinum) inhabiting a sewage lagoon at Reese AFB, Hurlwood, Texas, was found to have an exceptionally high rate of spontaneous tissue lesions. The population is composed of an estimated 28,000 large, reproductively mature larvae that are restricted to the lagoon. Only about 17% of the population metamorphoses normally. In contrast, tiger salamanders from uncontaminated lagoons in the same general vicinity metamorphose normally; however, no neoplasms were discovered in larvae sampled from the nonsewage lagoosn. N-nitrosamine analyses of water and tissue samples of larvae were negative. Polycyclic aromatic hydrocarbon analyses revealed traces of benzo[a]pyrene in the sludge; however, perylene, a constituent of jet fuel, was found in high concentration (300 ppb). These results indicate tat preylene, which was previously found not be tumorigenic to mice and rats, should be retested as a possible agent for nonmammalian species.


Myocardial tissue engineering using electrospun nanofiber composites.
Emerging trends for cardiac tissue engineering are focused on increasing the biocompatibility and tissue regeneration ability of artificial heart tissue by incorporating various cell sources and bioactive molecules. Although primary cardiomyocytes can be successfully implanted, clinical applications are restricted due to their low survival rates and poor proliferation. To develop successful cardiovascular tissue regeneration systems, new technologies must be introduced to improve myocardial regeneration. Electrospinning is a simple, versatile technique for fabricating nanofibers. Here, we discuss various biodegradable polymers (natural, synthetic, and combinatorial polymers) that can be used for fiber fabrication. We also describe a series of fiber modification methods that can increase cell survival, proliferation, and migration and provide supporting mechanical properties by mimicking micro-environment structures, such as the extracellular matrix (ECM). In addition, the applications and types of nanofiber-based scaffolds for myocardial regeneration are described. Finally, fusion research methods combined with stem cells and scaffolds to improve biocompatibility are discussed.


Insect-derived short proline-rich and murine cathelicidin-related antimicrobial peptides act synergistically on Gram-negative bacteria in vitro.
Organisms express a set of antimicrobial peptides (AMP) to protect the host against invading microbes by targeting their membranes or intracellular structures. Structurally optimized proline-rich AMPs (PrAMPs) are substantially more efficient in murine infection models than previously assumed from in vitro activities. Thus, we hypothesized that PrAMPs act synergistically with lytic AMPs intrinsically produced in hosts in response to an infection. Synergistic effects between lytic murine cathelicidin-related AMP (CRAMP) and apidaecin- and oncocin-derivatives were studied in chequerboard assays. Evaluation of fractional inhibitory concentration indices revealed synergies against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. CRAMP synergistically enhances the activity of proline-rich AMPs, which will allow evaluating their therapeutic potential more precisely in vitro.


Raw milk consumption and other early-life farm exposures and adult pulmonary function in the Agricultural Lung Health Study.
Literature suggests that early exposure to the farming environment protects against atopy and asthma; few studies have examined pulmonary function. We evaluated associations between early-life farming exposures and pulmonary function in 3061 adults (mean age=63) from a US farming population using linear regression. Childhood raw milk consumption was associated with higher FEV1 (β=49.5 mL, 95% CI 2.8 to 96.1 mL, p=0.04) and FVC (β=66.2 mL, 95% CI 13.2 to 119.1 mL, p=0.01). We did not find appreciable associations with other early-life farming exposures. We report a novel association between raw milk consumption and higher pulmonary function that lasts into older adulthood.


Weight cycling: more questions than answers.
Most men and women who attempt to lose weight will regain any weight that is lost. This cycle of weight loss and regain - referred to as weight cycling is a recurrent phenomenon for many patients. With the increased frequency of obesity and the increased prescriptions for weight-loss practices without an associated increase in the success of weight-loss maintenance, the concerns about weight cycling have grown. Recent literature has focused on the possible physiologic and psychologic hazards of weight cycling. Review of both human and animal studies indicates no conclusive evidence about harmful effects of weight cycling. Most studies show no adverse effects on metabolism. Some observational studies indicate an association between variations in body weight and increased morbidity and mortality but do not distinguish between voluntary and involuntary weight-loss events. The studies of psychologic hazards have been limited, and little convincing information is available. Without more compelling evidence of the risks of weight cycling, warnings overriding safe, effective weight-loss treatments for the obese are unwarranted. Appropriately designed studies are urgently needed to assess the long-term efficacy of procedures and treatments that promote weight-loss maintenance and to provide further analyses of the effects of weight cycling.


The combination of plant translational enhancers and terminator increase the expression of human glucocerebrosidase in Nicotiana benthamiana plants.
Gaucher's disease is a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCase). It is currently treated by enzyme replacement therapy using recombinant GCase expressed in mammalian cells. Plant production systems are among the most attractive alternatives for pharmaceutical protein production due to such advantages as low-cost, high-scalability, and safety from human pathogen contamination. Because of its high biomass yield, Nicotiana benthamiana could be an economical recombinant GCase production system. In this study, a translational enhancer and suitable terminator were utilized to obtain a powerful expression system for GCase production in N. benthamiana plants. Six plasmid constructs were used. The highest activity of 44.5units/mg protein (after subtraction of endogenous glucosidase activity of the wild-type plant) was observed in transgenic plants transformed with pAt-GC-HSP combined with a 5' untranslated region of the Arabidopsis alcohol dehydrogenase gene with the Arabidopsis heat shock protein terminator. These transgenic plant lines could pave the way to a stable plant-production system for low-cost, high-yield human GCase production.


The effect of heating on the expression and function of CD-2 molecules on human T-lymphocytes.
CD-2 molecules on the surface of human T-lymphocytes endow these cells with the capacity of binding sheep (SRBC) and human red blood cells (HRBC). It has recently become clear that they play an important role in the regulation of T-cell functions. The aim of the present study was to analyze the effect of heating at 45 degrees C for 1 hour on the capacity of human T-lymphocytes to bind SRBC and HRBC and to stain with CD-2 monoclonal antibody. Heating of human peripheral blood lymphocytes (PBL), thymus cells, or cells of the HD-MAR T-cell line drastically reduced their capacity of forming rosettes with SRBC. Heating of human thymus and HD-MAR cells also abrogated the formation of rosettes with HRBC. In contrast, the proportion of cells stained by high concentrations of CD-2 MoAb was reduced by only about 10-15%. Using radioiodine-labeled CD-2 MoAb, heating was found to reduce the number of cell surface E-receptors by 42% on PBL and by 27% on HD-MAR cells. The molecular weight of CD-2 molecules present on heated T-cells was identical with that of E-receptors on unheated cells. Heating was found to abolish antibody-induced capping of CD-2 molecules. Thus, heat treatment of human T-cells resulted in a moderate reduction in the number of cell-surface CD-2 molecules and in impaired mobility of CD-2 molecules in the membrane. It remains possible that in addition heating may affect the functional integrity of E-receptors or induce metabolic alterations detrimental for rosette formation.


Towards Extending Solar Cell Lifetimes: Addition of a Fluorous Cation to Triple Cation-Based Perovskite Films.
Organohalide perovskites have emerged as highly promising replacements for thin-film solar cells. However, their poor stability under ambient conditions remains problematic, hindering commercial exploitation. The addition of a fluorous-functionalized imidazolium cation during the preparation of a highly stable cesium-based mixed perovskite material Cs0.05 (MA0.15 FA0.85 )0.95 Pb(I0.85 Br0.15 )3 (MA=methylammonium; FA=formamidinium) has been shown to influence its stability. The resulting materials, which vary according to the amount of the fluorous-functionalized imidazolium cation present during fabrication, display a prolonged tolerance to atmospheric humidity (>100 days) along with power conversion efficiencies exceeding 16 %. This work provides a general route that can be implemented in a variety of perovskites and highlights a promising way to increase perovskite solar cell stability.


The effect of nifedipine on oral contraceptive-induced hypertension in rats.
Administration of oral contraceptive (OC) steroids is associated with an increased risk of developing hypertension, although the mechanisms underlying this effect are not well established. This study therefore sought to investigate the effect of L-type calcium channel blocker, nifedipine on OC-induced hypertension. Female Sprague-Dawley rats received OC (norgestrel/ethinyloestradiol) and/or nifedipine orally for 10 weeks. . Blood pressure and heart rate were thereafter recorded under anaesthesia from the femoral artery with a Grass Polygraph 7D model, whereas plasma and urinary Na+ and K+ concentrations were measured using a flame photometer. The stable oxidation products of nitric oxide, urinary nitrite/nitrate (NO) were measured in urine by means of the brucine method. OC administration led to significant (p<0.05) increases in blood pressure and plasma Na+, and decreases in body weight, food and water consumption, excretion of Na+ and NO. Concomitant treatment with nifedipine significantly (p<0.05) abrogated the alterations induced by OC administration. This study provides evidence that the development of OC-induced hypertension is prevented by calcium channel blockade via improved renal handling of sodium and nitric oxide. The finding confirms the involvement of calcium channels in OC hypertension.


Synthesis, crystal structure and antifungal activity of a divalent cobalt(II) complex with uniconazole.
Azole compounds have attracted commercial interest due to their high bactericidal and plant-growth-regulating activities. Uniconazole [or 1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pent-1-en-3-ol] is a highly active 1,2,4-triazole fungicide and plant-growth regulator with low toxicity. The pharmacological and toxicological properties of many drugs are modified by the formation of their metal complexes. Therefore, there is much interest in exploiting the coordination chemistry of triazole pesticides and their potential application in agriculture. However, reports of complexes of uniconazole are rare. A new cobalt(II) complex of uniconazole, namely dichloridotetrakis[1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl-κN(4))pent-1-en-3-ol]cobalt(II), [CoCl2(C15H18ClN3O)4], was synthesized and structurally characterized by element analysis, IR spectrometry and X-ray single-crystal diffraction. The crystal structural analysis shows that the Co(II) atom is located on the inversion centre and is coordinated by four uniconazole and two chloride ligands, forming a distorted octahedral geometry. The hydroxy groups of an uniconazole ligands of adjacent molecules form hydrogen bonds with the axial chloride ligands, resulting in one-dimensional chains parallel to the a axis. The complex was analysed for its antifungal activity by the mycelial growth rate method. It was revealed that the antifungal effect of the title complex is more pronounced than the effect of fungicide uniconazole for Botryosphaeria ribis, Wheat gibberellic and Grape anthracnose.


Post-menopausal hormone replacement therapy, coronary heart disease and plasma lipoproteins.
At least 20 million postmenopausal women worldwide now use some form of hormone replacement therapy. This figure is increasing because the resistance of the medical community to these therapies is diminishing and because of increasing acknowledgement of the benefits of such therapies on the cardiovascular system. This is a remarkable development for a medication originally used to relieve menopausal symptoms such as hot flushes and to prevent bone loss. Although several mechanisms are now accepted to be involved in this protection from cardiovascular disease, changes in plasma lipoproteins remain a major area of research interest. The main issue in this field, whether the addition of a progestogen to postmenopausal oestrogen ('combined therapy') will diminish the benefits on the cardiovascular system, remains unresolved, but combined therapies have now been formulated that minimize the potentially detrimental effects of progestogens on plasma lipoproteins. Recent findings of interest include the effects of these therapies on plasma lipoprotein (a) concentration and on LDL particle size. Studies of the mechanisms behind such changes are needed.


Antibody to Mac-1 or monocyte chemoattractant protein-1 inhibits monocyte recruitment and promotes tumor growth.
Human tumors are frequently infiltrated by numerous monocytes/macrophages, which can be found within the tumor mass (intratumoral) or surrounding the tumor (peritumoral). The functional role that these monocytes/macrophages play in tumor growth is controversial. To address this issue we inhibited intratumoral monocyte/macrophage recruitment with mAbs that either blocked integrin function or neutralized a tumor-produced chemotactic protein. Both treatments significantly increased tumor formation and accelerated tumor growth. Surprisingly, the same results were obtained when recruitment of peritumoral or intratumoral monocytes/macrophages was blocked. Our findings are contrary to one of the purported roles of monocytes/macrophages, particularly in the peritumoral area, since we found no evidence for monocyte/macrophage-supported tumor growth. These results provide direct evidence that intratumoral as well as peritumoral monocytes/macrophages act to limit tumor size in the early stages following tumor inoculation and provide a mechanism that accounts for monocyte/macrophage recruitment to human tumors.


Biomechanical model-based deformable registration of MRI and histopathology for clinical prostatectomy.
A biomechanical model-based deformable image registration incorporating specimen-specific changes in material properties is optimized and evaluated for correlating histology of clinical prostatectomy specimens with in vivo MRI. In this methodology, a three-step registration based on biomechanics calculates the transformations between histology and fixed, fixed and fresh, and fresh and in vivo states. A heterogeneous linear elastic material model is constructed based on magnetic resonance elastography (MRE) results. The ex vivo tissue MRE data provide specimen-specific information for the fresh and fixed tissue to account for the changes due to fixation. The accuracy of the algorithm was quantified by calculating the target registration error (TRE) by identifying naturally occurring anatomical points within the prostate in each image. TRE were improved with the deformable registration algorithm compared to rigid registration alone. The qualitative assessment also showed a good alignment between histology and MRI after the proposed deformable registration.


Pancreatic Stellate Cells and Metabolic Alteration: Physiology and Pathophysiology.
Pancreatic stellate cells play a pivotal role in the development of pancreatic fibrosis. A wide variety of external stimuli can cause PSC activation accompanied by metabolic changes, which alters the tissue microenvironment by producing extracellular matrix proteins, cytokines, growth factors, and other mediators. Several metabolites aggravate fibrosis and inflammation by acting as key activating factors for PSCs. In other words, PSCs sense systemic metabolic changes. The detrimental effects of PSC activation on normal pancreatic cells, especially islet cells, further complicate metabolic imbalance through the dysregulation of glucose metabolism. PSC activation promotes cancer by altering the metabolism in pancreatic cancer cells, which collaborate with PSCs to efficiently adapt to environmental changes, promoting their growth and survival. This collaboration also contributes to the acquisition of chemoresistance. PSCs sequester chemotherapeutic agents and produce competing molecules as additional resistance mechanisms. The application of these metabolic targets for novel therapeutic strategies is currently being explored. This mini-review summarizes the role of PSCs in metabolic regulation of normal and cancerous cells.


Studies related to the metabolism of anabolic steroids in the horse: 19-nortestosterone.
1. The metabolism of 19-nortestosterone in a cross-bred horse has been studied using 14C-labelled material. 2. Two neutral metabolites isolated from urinary extracts by column chromatography were identified as isomers of 3-hydroxyestran-17-one and estrane-3,17-diol by g.l.c.-mass spectrometry. 3. The stereochemistry of the two metabolites has been investigated by comparison of the retention times of their trimethylsilyl derivatives with those of standard steroids of known configuration.


Melittin selectively activates capsaicin-sensitive primary afferent fibers.
Whole bee venom (WBV)-induced pain model has been reported to be very useful for the study of pain. However, the major constituent responsible for the production of pain by WBV is not apparent. Intraplantar injection of WBV and melittin dramatically reduced mechanical threshold, and increased flinchings and paw thickness. In behavioral experiments, capsaicin pretreatment almost completely prevented WBV- and melittin-induced reduction of mechanical threshold and flinchings. Intraplantar injection of melittin increased discharge rate of dorsal horn neurons only with C fiber input from peripheral receptive field, which was completely blocked by topical application of capsaicin to sciatic nerve. These results suggest that both melittin and WBV induce nociceptive responses by selective activation of capsaicin-sensitive afferent fibers.


Dynamic Insights on Surgical Activity in a New Modern Warfare: The French Role 2 in Bangui, Central African Republic.
In December 2013, France deployed more than 2,000 soldiers in Central African Republic with two main missions, to restore security and to improve the humanitarian situation. The objectives of this article were to analyze the surgical activity of forward surgical teams in Central African Republic over 2 years and to discuss features of training for deployed surgeons. From December 5, 2013, to September 30, 2015, we retrospectively reviewed the electronic surgical database. Surgical activity was described as patient status, type of lesion, surgical procedures performed, and anatomic regions involved. During this study period, 431 surgical procedures were performed on 401 patients; 66% of the patients were civilians, 26% French soldiers, and 11% foreign soldiers. Surgical procedures were divided into 34% orthopedic activity and 66% general surgery activity. Orthopedic activity was mainly performed during the first months of the operation Sangaris, whereas general surgery occurred after summer 2014 with a return to peacetime. Our study demonstrated original and dynamic insights into the nature of surgical activity throughout the operation with mainly orthopedic surgery during the initial deployment for management of combat casualties and general surgery later, dedicated to elective surgery for local citizens. These data should enhance staffing, training, and deployment of future surgical teams in combat settings with continuous training programs to maintain specific competences, especially in cases of low surgical activity, such as virtual learning or e-learning that could be developed in the future.


Phosphorus-Doped Iron Nitride Nanoparticles Encapsulated by Nitrogen-Doped Carbon Nanosheets on Iron Foam In Situ Derived from Saccharomycetes Cerevisiae for Electrocatalytic Overall Water Splitting.
It is vitally essential to propose a novel, economical, and safe preparation method to design highly efficient electrocatalysts. Herein, phosphorus-doped iron nitride nanoparticles encapsulated by nitrogen-doped carbon nanosheets are grown directly on the iron foam substrate (P-Fe3 N@NC NSs/IF) by in situ deriving from Saccharomycetes cerevisiae (S. cerevisiae), where anion elements of C, N, and P all from S. cerevisiae replace the hazardous CH4 , NH3 , and H3 P. The diffusion pattern of N, P in S. cerevisiae and contact form between metal and S. cerevisiae observably affect the composition and phase of the product during high-temperature calcination. The obtained P-Fe3 N@NC NSs/IF demonstrates superior electrocatalytic performance for the hydrogen evolution reaction and oxygen evolution reaction, also satisfying durability. Theoretical calculation confirms that Fe sites of P-Fe3 N serve as the active center, and N sites and P doping regulate the hydrogen binding strength to enhance catalytic ability. Additionally, the two-electrode electrolyzer assembled by P-Fe3 N@NC NSs/IF as both anode and cathode electrodes needs only 1.61 V to reach 10 mA cm-2 for overall water splitting with a superb stability. The S. cerevisiae-based process presents a feasible approach for synthesis of nitrides, carbides, phosphides, and electrocatalytic applications.


Alcohol Use Disorder Treatment in Sexually and Gender Diverse Patients: A Retrospective Cohort Study.
Objective: While sexually and gender diverse (SGD) people have higher odds of alcohol use disorder (AUD) compared to heterosexual and cisgender people, AUD treatment access and use disparities are not well characterized. The purpose of this study is to assess differences in AUD treatment among SGD versus non-SGD populations. Methods: A retrospective cohort study was performed using data from a federally qualified health center electronic health record system in Boston, Massachusetts. Patients were 18 years or older with an International Classification of Diseases (ICD)-9 or ICD-10 AUD diagnosis and any clinic visit from January 2013 until June 2021 (N = 3,607). Treatment for AUD was identified using binary variables for medication prescription orders and visits for AUD. Results: Among patients identifying as lesbian/gay, 6.9% had an AUD diagnosis, as compared to 2.6% of patients identifying as straight/heterosexual (P < .001). The prevalence of AUD was higher in the gender diverse group as compared to the cisgender group (5.5% vs 4.4%, P < .001). There were no significant differences in receipt of a prescription for injectable naltrexone, acamprosate, or disulfiram between SGD and non-SGD patients. For oral naltrexone, 16.1% of sexually diverse patients received a prescription, as compared to 9.8% of straight/heterosexual patients (P < .001). For visits, both the straight/heterosexual cohort and the cisgender cohorts had the lowest proportion of AUD-related pharmacotherapy and individual psychotherapy visits, as compared to SGD cohorts. Conclusions: SGD patients had higher proportions of AUD diagnosis and AUD care utilization through behavioral health as compared to non-SGD patients.


Whey protein isolate polydispersity affects enzymatic hydrolysis outcomes.
The effects of heat-induced denaturation of whey protein isolate (WPI) on the enzymatic breakdown of α-La, caseinomacropeptide (CMP), β-Lg A and β-Lg B were observed as hydrolysis proceeded to a 5% degree of hydrolysis (DH) in both unheated and heat-treated (80 °C, 10 min) WPI dispersions (100 g L(-1)). Hydrolysis of denatured WPI favoured the generation of higher levels of free essential amino acids; lysine, phenylalanine and arginine compared to the unheated substrate. LC-MS/MS identified 23 distinct peptides which were identified in the denatured WPI hydrolysate - the majority of which were derived from β-Lg. The mapping of the detected regions in α-La, β-Lg, and CMP enabled specific cleavage points to be associated with certain serine endo-protease activities. The outcomes of the study emphasise how a combined approach of substrate heat pre-treatment and enzymology may be used to influence proteolysis with attendant opportunities for targeting unique peptide production and amino acid release.


Role of the p66Shc isoform in insulin-like growth factor I receptor signaling through MEK/Erk and regulation of actin cytoskeleton in rat myoblasts.
To investigate the role of Shc in IGF action and signaling in skeletal muscle cells, Shc protein levels were reduced in rat L6 myoblasts by stably overexpressing a Shc cDNA fragment in antisense orientation (L6/Shcas). L6/Shcas myoblasts showed marked reduction of the p66Shc protein isoform and no change in p52Shc or p46Shc proteins compared with control myoblasts transfected with the empty vector (L6/Neo). When compared with control, L6/Shcas myoblasts demonstrated 3-fold increase in Erk-1/2 phosphorylation under basal conditions and blunted Erk-1/2 stimulation by insulin-like growth factor I (IGF-I), in the absence of changes in total Erk-1/2 protein levels. Increased basal Erk-1/2 activation was paralleled by a greater proportion of phosphorylated Erk-1/2 in the nucleus of L6/Shcas myoblasts in the absence of IGF-I stimulation. The reduction of p66Shc in L6/Shcas myoblasts resulted in marked phenotypic abnormalities, such as rounded cell shape and clustering in islets or finger-like structures, and was associated with impaired DNA synthesis in response to IGF-I and lack of terminal differentiation into myotubes. In addition, L6/Shcas myoblasts were characterized by complete disruption of actin filaments and cell cytoskeleton. Treatment of L6/Shcas myoblasts with the MEK inhibitor PD98059 reduced the abnormal increase in Erk-1/2 activation to control levels and restored the actin cytoskeleton, re-establishing the normal cell morphology. Thus, the p66Shc isoform exerts an inhibitory effect on the mitogen-activated protein kinase signaling pathway in rodent myoblasts, which is necessary for maintenance of IGF responsiveness of the MEK/Erk pathway and normal cell phenotype.


Increasing Number and Volume of Cavitary Lesions on Chest Computed Tomography Are Associated With Prolonged Time to Culture Conversion in Pulmonary Tuberculosis.
Cavitary lesions (CLs) primarily identified by chest x-ray (CXR) have been associated with worse clinical outcomes among patients with pulmonary tuberculosis (PTB). Chest computed tomography (CT), which has better resolution and increased sensitivity to detect lung abnormalities, has been understudied in PTB patients. We compared detection of CLs by CT and CXR and assessed their association with time to sputum culture conversion (tSCC). This was a retrospective cohort study of 141 PTB patients who underwent CT. We used multivariate Cox proportional hazards models to evaluate the association between CLs on CXR and the number and single largest volume of CLs on CT with tSCC. Thirty (21%) and 75 (53%) patients had CLs on CXR and CT, respectively. CT detected cavities in an additional 44 patients (31%) compared with CXR. After multivariable adjustment, we observed a negative association between CLs and tSCC, with an adjusted hazard ratio (aHR) of 0.56 (95% confidence interval [CI], 0.32 to 0.97) for single CLs and 0.31 (95% CI, 0.16 to 0.60) for multiple CLs present on CT. Patients with a CL volume ≥25 mL had a prolonged tSCC (aHR, 0.39; 95% CI, 0.21 to 0.72). CLs on CXR were not associated with increased tSCC after multivariable adjustment. CT detected a larger number of cavities in patients with PTB relative to CXR. We observed an association between increasing number and volume of CLs on CT and delayed tSCC independent of sputum microscopy result. Our findings highlight a potential role for CT in the clinical and research setting as a tool to risk-stratify patients with PTB.


Differential use of transcription activation function 2 domain of the vitamin D receptor by 1,25-dihydroxyvitamin D3 and its A ring-modified analogs.
Analogs of 1,25-dihydroxyvitamin D3 (1,25D3) can be used to elucidate details of vitamin D receptor (VDR) activation. The A ring-modified analog, (TN-2) has 15-fold less affinity for VDR, but its transcriptional activity is diminished 1000-fold. Likewise, the ability of TN-2 to induce a protease-resistant conformation in VDR is 1/1000 that of 1,25D3. The stability of the VDR-TN-2 complexes is also significantly lower than VDR-1,25D3 complexes. Mapping the VDR-binding site of TN-2 showed that it had a significantly greater requirement for transcription activation function 2 (AF-2) residues than 1,25D3 did. These results suggest that the increased requirement for AF-2 residues that was induced by the A ring modifications is associated with diminished receptor activation. To determine whether restoring the potency of TN-2 by additional structural modifications would change the requirements for AF-2 residues, we synthesized hybrid analogs with 1beta-hydroxymethyl-3-epi groups and with dimethyl groups at positions 26 and 27 of the side chain, without or with a double bond between CD ring positions 16 and 17. We found that the side chain modification enhanced transcriptional activity 150-fold, increased the ability of the receptor to form a protease-resistant conformation 100-fold, and stabilized the VDR-analog complexes. The addition of the 16-ene group further reduced the analog's dissociation rate and increased its potency in the protease assays. These functional changes in the hybrid analogs were associated with a significant reduction in interaction with AF-2 residues. We conclude that there is an inverse relationship between analogs' potencies and their interaction with AF-2 residues of VDR.


Alcohol consumption and risk of cataract extraction: a prospective cohort study of women.
To investigate the association between alcohol consumption and the risk of cataract extraction. Population-based prospective cohort study. A total of 34,713 women participating in the Swedish Mammography Cohort, age 49 to 83 years, completed in 1997 a self-administered questionnaire about alcohol, smoking, and other lifestyle factors. The women were followed from September 1997 through September 2004. The cohort was matched with registers of cataract extraction from the study area. Incident surgical extraction of age-related cataract. During 84 months of follow-up, we found 3587 incident cases of age-related cataract extraction. Compared with never drinkers, the relative risk of cataract extraction among current drinkers was 1.11 (95% confidence interval [CI] 1.02-1.21) after adjustment for age and other potential risk factors. In multivariate analysis, an increment of 13 g alcohol intake per day (corresponding to 1 drink = 330 ml of beer, 150 ml of wine, or 45 ml of liquor) was associated with a 7% increased risk of cataract extraction (relative risk, 1.07; 95% CI 1.02-1.12). Mean age at cataract extraction among nonsmoking women who used alcohol was 75 years, compared with 77.6 years among never drinkers. These prospective data suggest that daily use of >/=1 alcoholic drinks was associated with a modest increase of risk for cataract extraction. The risk increased with increasing alcohol consumption.


[A Case of Combined Use of Endoscopic Submucosal Dissection and Transanal Excision for Early Rectal Cancer with Extension into the Anal Canal].
A 77-year-old woman visited our hospital after noticing bleeding during defecation. Lower gastrointestinal endoscopy revealed an early rectal tumor with extension into the anal canal, thus transanal excision was performed. However, histopathological examination revealed a positive surgical margin, therefore, additional transanal excision was performed with endoscopic submucosal dissection, and the residual cancer tissue was completely resected. At one year after surgery, no recurrence has been observed.


Endemic goiter in Ethiopian Jews--possible pathogenetic factors.
Goiter size, thyroid function tests and thyroid cytology were studied in 100 immigrant Ethiopian Jews, 1-12 months after arrival in Israel on Operation Solomon (1991), who were referred for evaluation of goiter. Female-to-male ratio was 2.2:1. Hypothyroidism was rare (1%) whereas hyperthyroidism was frequently diagnosed (11%). Elevated thyroglobulin (TG) serum levels were found in 36% of the patients. Antithyroid antibodies were not detected. Thyroid cytology revealed rich colloid goiters in all patients. Thyroid carcinomata and chronic lymphocytic thyroiditis were not diagnosed. Both hyperthyroidism and elevated TG levels were found only in female patients and were equally distributed in patients maintained on either Israeli or Ethiopian diets. It is suggested that the major factors in the pathogenesis of endemic goiter in Ethiopian Jews are genetic and/or food goiterogens, with only a minor role for iodine deficiency.


Distributed Coding of Evidence Accumulation across the Mouse Brain Using Microcircuits with a Diversity of Timescales.
The gradual accumulation of noisy evidence for or against options is the main step in the perceptual decision-making process. Using brain-wide electrophysiological recording in mice (Steinmetz et al., 2019), we examined neural correlates of evidence accumulation across brain areas. We demonstrated that the neurons with drift-diffusion model (DDM)-like firing rate activity (i.e., evidence-sensitive ramping firing rate) were distributed across the brain. Exploring the underlying neural mechanism of evidence accumulation for the DDM-like neurons revealed different accumulation mechanisms (i.e., single and race) both within and across the brain areas. Our findings support the hypothesis that evidence accumulation is happening through multiple integration mechanisms in the brain. We further explored the timescale of the integration process in the single and race accumulator models. The results demonstrated that the accumulator microcircuits within each brain area had distinct properties in terms of their integration timescale, which were organized hierarchically across the brain. These findings support the existence of evidence accumulation over multiple timescales. Besides the variability of integration timescale across the brain, a heterogeneity of timescales was observed within each brain area as well. We demonstrated that this variability reflected the diversity of microcircuit parameters, such that accumulators with longer integration timescales had higher recurrent excitation strength.


Lipid metabolic reprogramming of hepatic CD4+ T cells during SIV infection.
While liver inflammation is associated with AIDS, little is known so far about hepatic CD4+ T cells. By using the simian immunodeficiency virus (SIV)-infected rhesus macaque (RM) model, we aimed to characterize CD4+ T cells. The phenotype of CD4+ T cells was assessed by flow cytometry from uninfected (n = 3) and infected RMs, with either SIVmac251 (n = 6) or SHIVSF162p3 (n = 6). After cell sorting of hepatic CD4+ T cells, viral DNA quantification and RNA sequencing were performed.Thus, we demonstrated that liver CD4+ T cells strongly expressed the SIV coreceptor, CCR5. We showed that viremia was negatively correlated with the percentage of hepatic effector memory CD4+ T cells. Consistent with viral sensing, inflammatory and interferon gene transcripts were increased. We also highlighted the presence of harmful CD4+ T cells expressing GZMA and members of TGFB that could contribute to fuel inflammation and fibrosis. Whereas RNA sequencing demonstrated activated CD4+ T cells displaying higher levels of mitoribosome and membrane lipid synthesis transcripts, few genes were related to glycolysis and oxidative phosphorylation, which are essential to sustain activated T cells. Furthermore, we observed lower levels of mitochondrial DNA and higher levels of genes associated with damaged organelles (reticulophagy and mitophagy). Altogether, our data revealed that activated hepatic CD4+ T cells are reprogrammed to lipid metabolism. Thus, strategies aiming to reprogram T cell metabolism with effector function could be of interest for controlling viral infection and preventing liver disorders.IMPORTANCEHuman immunodeficiency virus (HIV) infection may cause liver diseases, associated with inflammation and tissue injury, contributing to comorbidity in people living with HIV. Paradoxically, the contribution of hepatic CD4+ T cells remains largely underestimated. Herein, we used the model of simian immunodeficiency virus (SIV)-infected rhesus macaques to access liver tissue. Our work demonstrates that hepatic CD4+ T cells express CCR5, the main viral coreceptor, and are infected. Viral infection is associated with the presence of inflamed and activated hepatic CD4+ T cells expressing cytotoxic molecules. Furthermore, hepatic CD4+ T cells are reprogrammed toward lipid metabolism after SIV infection. Altogether, our findings shed new light on hepatic CD4+ T cell profile that could contribute to liver injury following viral infection.


Adrenomedullin promotes the odontogenic differentiation of dental pulp stem cells through CREB/BMP2 signaling pathway.
Adrenomedullin (AM) could promote the proliferation, the odontogenic differentiation and inhibit the apoptosis of dental pulp stem cells (DPSCs). AM in combination with DPSCs may be an effective strategy for pulp repair. However, there was no report on the mechanisms of AM in the odontogenic differentiation of DPSCs. The aim of this study is to investigate the molecular mechanisms through which AM promotes the odontogenic differentiation of DPSCs. Freshly extracted wisdom teeth were obtained from 27 patients. Cells at passage 3 to passage 5 were used in this study. DPSCs were treated with or without 10-7 M AM in Dulbecco's modified Eagle's medium culture, and then the accumulated calcium deposition was analyzed after 21 days by using alizarin red S staining. Odontogenic differentiation markers were determined by western blot analysis and quantitative real-time PCR. Western blot analysis results showed that AM had the capability of promoting the odontogenic differentiation of DPSCs and AM could enhance the phosphorylation of CREB and up-regulate the expression of BMP2. H89 is a CREB inhibitor which can inhibit the odontogenic differentiation of DPSCs through inhibiting the phosphorylation of CREB. Noggin could inhibit the odontogenic differentiation of DPSCs through inhibiting the activity of BMP2. These results indicated that AM could promote the odontogenic differentiation of DPSCs by upregulating the expression of BMP2 through the CREB signaling pathway.