Pacemaker dependence in transient high-grade atrioventricular block.
In a prospective study 16 patients who had been given a pacemaker because of symptomatic high-grade atrioventricular block and whose conduction had been recovered were checked for their dependence on the pacemaker. During a follow-up time ranging from 32 to 158 months (median 62 months) six patients proved to be dependent on the device owing to the development of recurrent stable high-grade atrioventricular block. The subsequent return of atrioventricular block was evidently not associated with etiology, age, sex, ECG-pattern or length of follow-up period. Five additional patients equipped with a bradycardia-indicating pacemaker all proved to be pacemaker-dependent after a follow-up time ranging from 1-20 months (median 7 months), even though atrioventricular conduction had recovered and its presence had been confirmed at regular outpatient checks. It is thus evident that the conventional clinical methods are of limited value for examining the course of conduction defect and assessing the prognosis for patients whose spontaneous cardiac activity has returned after periods of symptomatic high-grade atrioventricular block. When a bradycardia-indicating pacemaker was furnished, pacemaker dependence was demonstrated in most of the patients whose atrioventricular conduction had recovered. This confirms that pacing introduced because of symptomatic high-grade atrioventricular block should not be discontinued even if a conducted heart rhythm has been established and maintained for long periods.


Antimicrobial activity of protoanemonin, a lactone from ranunculaceous plants.
Protoanemonin, a component of Ranunculus bulbosus, was tested as an antifungal agent on selected strains of dermatophytes and yeasts. The minimum inhibitory concentrations ranged from 2.0 to 7.5 X 10(-4) M and the minimum lethal concentrations from 3.8 X 10(-4) M to greater than 1.0 X 10(-3) M. The most sensitive dermatophyte tested was Epidermophyton floccosum, and the most sensitive yeast Rhodotorula glutinis. The effects of different culture media and of light on the sensitivity of Rhodotorula glutinis to protoanemonin were also tested. Structural analogies between protoanemonin and other cytotoxic unsaturated lactones, and the reversal by the amino acid cysteine of the antifungal action suggest a possible mechanism of action.


Errors in the Diagnosis of Stroke-Tales of Common Stroke Mimics and Strokes in Hiding.
Stroke mimics are some of the common causes of misdiagnosis of stroke, with an attendant surfeit of finances and resources. We attempt to discuss some of the common neurological conditions mimicking stroke in the emergency. We reviewed the articles in English discussing stroke mimics in the last 5 years of publication. We discuss the most common causes of stroke mimics encountered in neurological practice. In this short communication, we shall focus on the discussion of the diagnostic pitfalls and clinical clues that will help distinguish mimics from a true stroke.


Coordination of the nuclear and cytoplasmic activities of p53 in response to DNA damage.
The tumor suppressor p53 plays a key role in the cellular response to various stresses. Most previous studies have focused on either the nuclear or cytoplasmic proapoptotic functions of p53, ignoring the combination of both functions. To explore how the two functions of p53 are coordinated in the DNA damage response via computer simulation, we construct a model for the p53 network comprising coupled positive and negative feedback loops involving p53, Mdm2, and Akt, as well as PUMA and Bax. In our model p53 is stabilized and accumulates in the nucleus and cytoplasm upon DNA damage. Nuclear p53 induces expression of Mdm2, PTEN, PUMA, and Bax. Cytoplasmic p53 is then released from the p53.Bcl-xL complex by PUMA to activate Bax directly. We find that the switching between low and high protein levels underlies the decision between cell survival and death. Moreover, a balance between the nuclear and cytoplasmic p53 levels and appropriate levels of Akt and PUMA are required for reliable cell fate decision. Our results indicate that coordination of the transcription-dependent and -independent activities of p53 is important in determining cellular outcomes. These findings advance our understanding of the mechanism for p53-mediated cellular responses and provide clues to p53-based cancer therapy.


Development of islet-like cell clusters after pancreas transplantation in the spontaneously diabetic Torri rat.
Pancreas transplantation (PTx) has evolved as a clinical therapy to achieve sustained euglycemia. However, it remains unclear if naive diseased islets of the pancreas benefit from the avoidance of glucose toxicity by PTx. In the present study, using an animal model of type 2 diabetes, the Spontaneously Diabetic Torii (SDT; RT1a) rat, we syngeneically transplanted nondiabetic 10-week-old pancreaticduodenal grafts into diabetic 25-week-old recipients. In the control SDT rats that received no treatment, hyperglycemia developed with a mean onset time of 25 +/- 3.9 weeks of age. Few normal islet cells were found from 25 weeks and none at 40 weeks. However, in the PTx rats, the onset age (graft age) of diabetes was significantly prolonged (47 +/- 18.2 weeks). Moreover, we found that the beta-cell mass was significantly increased in the naive pancreases of 40-week-old PTx recipients (PTx40-naive). Interestingly, islet-like cell clusters of varying size were found close to ductal structures of PTx40-naive pancreases, suggesting that these cells are derived from ductal cells. Furthermore, pancreatic and duodenal homeobox factor-1 (PDX-1) was more clearly expressed in the nuclei of PTx40-naive pancreatic islet-like cell clusters. Our results demonstrate the development of duct-derived beta cells in the pancreas of type 2 diabetic recipients after PTx.


Uterocutaneous fistula due to held placenta in a low resource setting.
Postcesarean section complication rate is higher in LMIC (Low and Middle Income Countries) due to lack of resources and specialists availability. A completely or incompletely held infected placenta might underlie a dehiscent cesarean section wound. Humanitarian and local surgeons should consider this differential diagnosis and be ready to practice hysterectomies when needed.


Long-term treatment with galcanezumab in patients with chronic migraine: results from the open-label extension of the REGAIN study.
Galcanezumab, a monoclonal antibody to calcitonin gene-related peptide, was found to be safe and efficacious for the preventive treatment of chronic migraine based on the randomized, placebo-controlled double-blind period of the REGAIN study. Long-term safety and efficacy were assessed in an open-label extension. Patients 18-65 years old with chronic migraine completing the 3-month double-blind period of REGAIN could enter a 9-month open-label extension (OLE; months 4-12). Upon entering the OLE, patients received a 240-mg galcanezumab loading dose, then 120 mg at the next month, with flexible dosing thereafter (120 or 240 mg/month). The primary efficacy measure was the mean change in the number of monthly migraine headache days from double-blind baseline to month 12. Other endpoints included response rates (based on percent reduction in monthly migraine headache days from double-blind baseline to month 12), safety and tolerability. Of patients who completed double-blind treatment, 1022 (99%) entered the OLE, with 81% completing month 12. From a baseline of 19.4 monthly migraine headache days at the beginning of the double-blind period, patients at month 12 in the previous placebo, 120-mg, and 240-mg galcanezumab groups had a mean change of -8.5, -9.0, and -8.0, respectively (SE = 0.43 to 0.55, within-group p's < .001). At month 12, the percentage of patients with ≥50% response was 57%, 57%, and 53%, respectively. Percentage with ≥75% response was 32%, 31%, and 30%, respectively. Percentage with 100% response was 8%, 6%, and 6%, respectively. There were no significant new safety findings during the open-label period. The incidence of discontinuation from the OLE due to adverse events was 5%. Galcanezumab was effective, safe, and well-tolerated, with high adherence, for up to 12 months of treatment in patients with chronic migraine. Clinicaltrials.gov identifier: NCT02614261; www.clinicaltrials.gov/ct2/show/NCT02614261.


Cross-reinstatement of mitragynine and morphine place preference in rats.
Kratom is a medicinal plant that exhibits promising results as an opiate substitute. However, there is little information regarding the abuse profile of its main psychoactive constituent, mitragynine (MG), particularly in relapse to drug abuse. Using the place conditioning procedure as a model of relapse, this study aims to evaluate the ability of MG to induce conditioned place preference (CPP) reinstatement in rats. To evaluate the cross-reinstatement effects, MG and morphine were injected to rats that previously extinguished a morphine- or MG-induced CPP. Following a CPP acquisition induced by either MG (10 and 30 mg/kg, i.p.) or morphine (10 mg/kg, i.p.), rats were subjected to repeated CPP extinction sessions. A low dose priming injection of MG or morphine produced a reinstatement of the previously extinguished CPP. In the second experiment of this study, a priming injection of morphine (1, 3 and 10 mg/kg, i.p.) dose-dependently reinstated an MG-induced CPP. Likewise, a priming injection of MG (3, 10 and 30 mg/kg, i.p.) was able to dose-dependently reinstate a morphine-induced CPP. The present study demonstrates a cross-reinstatement effect between MG and morphine, thereby suggesting a similar interaction in their rewarding motivational properties. The findings from this study also suggesting that a priming exposure to kratom and an opioid may cause relapse for a previously abused drug.


Circumferential location predicts the risk of high-grade dysplasia and early adenocarcinoma in short-segment Barrett's esophagus.
Whether early Barrett's neoplasia has a predilection for particular spatial locations in shorter segment disease is currently unknown. Anatomic factors may play a role in lesion location because of differing levels of mucosal acid exposure. To identify high-risk lesion locations, which has important implications for surveillance strategies. We interrogated a prospectively maintained database of patients who underwent endoscopic resection (ER) for Barrett's neoplasia at 2 Australian tertiary centers. Lesions targeted for ER were characterized and their location in the distal esophagus was noted as on a clock face. A Z test of proportions was used to test for deviation from uniformity in the distribution of lesions. Two Australian tertiary centers. Patients who underwent ER for Barrett's neoplasia. Lesion location in the distal oesophagus, resected specimen histology. A total of 146 consecutive patients had ER for biopsy-proven high-grade dysplasia or esophageal adenocarcinoma. A total of 75 patients had Barrett's segment length of 5 cm or less and a visible lesion. Five patients had 2 visible lesions giving a total of 80 lesions. ER of 66 lesions (82.5%) led to the identification of advanced pathology: 37 high-grade dysplasia (46%), 24 mucosal adenocarcinoma (30%), 5 submucosal adenocarcinoma (6%). Of a total of 80 lesions, 43 (53.8%) (95% CI, 42.9%-64.7%) were centered within the 2- to 5-o'clock arc, comprising 25% of the circumference. This area also accounted for 36 (54.5%) of the 66 lesions with advanced histology (95% CI, 42.5%-66.5%). All confidence intervals lie wholly above the 25% expected in a uniform circular distribution (P < .05). Observational study in a tertiary center. In Barrett's maximal segments of 5 cm or less, the 2- to 5-o'clock arc, accounts for approximately 50% of macroscopically visible lesions and associated early neoplasia. This finding has important implications for surveillance strategies.


Association of cytoskeletal proteins with newly formed acetylcholine receptor aggregates induced by embryonic brain extract.
Aggregates of acetylcholine receptors (AChR) in muscle cell membranes are associated with accumulations of certain cytoskeletal and peripheral membrane proteins. We treated cultured rat myotubes briefly with embryonic brain extract (EBX) to promote AChR aggregation and determined the distribution of several of these proteins at early stages of aggregation. EBX-treated and control cultures were stained with tetramethylrhodamine-alpha-bungarotoxin to identify AChR aggregates and were then frozen and sectioned on a cryostat. These sections were stained with primary antibodies and fluoresceinated secondary antibodies to localize cytoskeletal proteins. The distributions of AChRs and cytoskeletal proteins was examined qualitatively and analyzed by a semiquantitative assay. Qualitatively, the 43K protein had a distribution that was virtually identical to that of AChR in both control and EBX-treated cultures, and it always colocalized with early AChR aggregates. The 58K protein similarly colocalized with early AChR aggregates, but it was also in aggregate-free areas of muscle membrane. The association of vinculin with the aggregates was quantitatively similar to that of the 43K and 58K proteins, but, qualitatively, its distribution did not follow that of the AChR as closely. Like the 58K protein and vinculin, alpha-actinin, filamin, and actin were concentrated in AChR aggregates and were also enriched elsewhere. However, they were less closely associated with the aggregates, both quantitatively and qualitatively. These results show that AChR aggregates induced by EBX tend to be enriched in the same cytoskeletal proteins that are present at the neuromuscular junction in vivo and at AChR clusters formed at sites of cell-substrate adhesion in vitro. Semiquantitative analysis also revealed that the fractional area of the cell surface associated with vinculin, alpha-actinin, and the 58K protein was the same in controls and EBX-treated myotubes, although the area enriched in AChR and the 43K protein increased about three-fold upon EBX treatment. These results suggest that AChR aggregates may form preferentially in membrane regions that are already enriched in these proteins.


Benefit of early abdominal ultrasonography in non-surgical patients admitted to the emergency department: a pilot study.
Ultrasonography plays a decisive role in emergency patients. The primary aim of this study is to assess whether early emergency ultrasonography alters the length of stay. In a prospective study, patients admitted to the emergency department were divided into two groups. The first group underwent early abdominal ultrasonography (within 24 h after admission), and the second group underwent ultrasonography after more than 24 h. The two groups were compared in terms of length of stay, age, admission diagnosis, and number of further imaging techniques used. A subgroup analysis was carried out for admission diagnosis. One hundred and forty-five patients were included in the study. In terms of length of stay, no difference was seen between the first group (11.7 ± 11.4 days) and the second group (13.6 ± 11.0 days) (p = 0.1196). In the subgroups "abdominal pain" (p = 0.0333) and "cardiopulmonary disorders" (p = 0.0207), a shorter length of stay was associated with early ultrasonography, while in the subgroup "infectious disease/fever," the early ultrasonography group was associated with a prolonged length of stay (p = 0.0211). Early ultrasonography in our setting of emergency patients with a variety of different admission diagnoses did not shorten the length of stay, but the subgroups of patients with "abdominal pain" and "cardiopulmonary disorders" might have benefited from early ultrasonography.


Varp interacts with Rab38 and functions as its potential effector.
Varp, a novel protein containing a VPS9 domain and ankyrin repeats, can function as a guanine nucleotide exchange factor (GEF) of Rab21. We previously reported that Varp plays an important role in the regulation of endosome dynamics. To further investigate the function of Varp, a yeast two-hybrid screen was performed and Rab38 was identified as a Varp-associated protein. We demonstrate that Varp physically interacts with Rab38, and preferentially binds to the active GTP-bound form of Rab38 both in vitro and in vivo. Furthermore, Varp was shown to be recruited to Rab38-positive organelles in an ankyrin-repeat 1 (ANK1)-dependent manner. Our data demonstrate that Varp is a potential effector of Rab38. Together with our previous study, we propose Varp serves as both an effector and a GEF by interacting with different Rabs in mammalian cells.


Neonatal outcomes following different ovarian stimulation protocols in fresh single embryo transfer.
Previous studies suggested ovarian stimulation was associated with lower birth weight and higher risk of preterm delivery (PTD) from fresh embryo transfers (ETs). However, whether the increased risk differs between distinct ovarian stimulation protocols remains unknown. A retrospective cohort study of 38,220 singleton deliveries after fresh single ETs from 2007 to 2013 was conducted. Main outcomes were birth weight and gestational length. Compared with the natural cycle, all ovarian stimulation protocols were associated with a significantly increased risk for PTD, low birth weight (LBW) and small for gestational age (SGA). In subgroup analysis of maternal age under 35 years, luteal support using progesterone, and early cleavage ETs, the significant associations remained for LBW and SGA in gonadotropin-releasing hormone (GnRH) antagonist protocol and for LBW in GnRH agonist protocol. Ovarian stimulation using clomiphene citrate (CC) had the highest increased risks for LBW (Adjusted odds ratio [AOR], 1.58, 95% confidence interval [95% CI], 1.43-1.73) and SGA (AOR, 1.65, 95% CI, 1.50-1.82) compared with natural cycles, and was further associated with PTD and cesarean section. These findings suggest ovarian stimulation was associated with lower birth weight, and CC may have adverse effect on neonatal outcomes in fresh cycles.


Beyond a reasonable doubt? Bisphosphonates and atypical femur fractures.
In May 2011, we were privileged to debate on behalf of the ECTS and the ASBMR in a Clinical Debate hosted by the IBMS and the ECTS with the motion "Atypical femoral shaft fractures are a consequence of bisphosphonate therapy". The evidence presented for and against the motion is summarized and discussed in this joint commentary. The hypothetical chain of evidence between bisphosphonates, decreased toughness of bone, microcrack accumulation in man and atypical fractures is plausible but unproven. However, the combination of consistent clinical features (which may include a stress reaction at the site of maximum tensile load), a significant statistical association and a feasible biological mechanism gives grounds for caution especially as regards long term treatment in patients at low or moderate risk of osteoporotic fractures.


What It Takes to Solve the Hubble Tension through Modifications of Cosmological Recombination.
We construct data-driven solutions to the Hubble tension which are perturbative modifications to the fiducial ΛCDM cosmology, using the Fisher bias formalism. Taking as proof of principle the case of a time-varying electron mass and fine structure constant, and focusing first on Planck CMB data, we demonstrate that a modified recombination can solve the Hubble tension and lower S_{8} to match weak lensing measurements. Once baryonic acoustic oscillation and uncalibrated supernovae data are included, however, it is not possible to fully solve the tension with perturbative modifications to recombination.


Histone deacetyltransferase inhibitors Trichostatin A and Mocetinostat differentially regulate MMP9, IL-18 and RECK expression, and attenuate Angiotensin II-induced cardiac fibroblast migration and proliferation.
Histone acetylation/deacetylation plays a key role in the epigenetic regulation of multiple pro-fibrotic genes. Here we investigated the effects of histone deacetyltransferase (HDAC) inhibition on angiotensin (Ang)-II-induced pro-fibrotic changes in adult mouse cardiac fibroblasts (CF). CF express class I HDACs 1 and 2, and Ang-II induces their activation. Notably, silencing HDAC1 or HDAC2 attenuated Ang-II induced CF proliferation and migration. Under basal conditions, HDAC1 dimerizes with HDAC2 in CF and Ang-II reversed this interaction. Treatment with Trichostatin A (TSA), a broad-spectrum HDAC inhibitor, restored their physical association, and attenuated Ang-II-induced MMP9 expression, IL-18 induction, and extracellular matrix (collagen I, collagen III and fibronectin) production. Further, TSA inhibited Ang-II-induced MMP9 and Il18 transcription by blocking NF-κB and AP-1 binding to their respective promoter regions. By inhibiting Sp1 binding to RECK promoter, TSA reversed Ang-II-induced RECK suppression, collagen and fibronectin expression, and CF migration and proliferation. The class I-specific HDAC inhibitor Mocetinostat (MGCD) recapitulated TSA effects on Ang-II-treated CF. Together, these results demonstrate that targeting HDACs attenuates the pro-inflammatory and pro-fibrotic effects of Ang-II on CF.


Secondary implantation of implantable collamer lens (ICL) for correction of anisometropic hyperopia in a 3-year-old pseudophakic child.
We report the first case of secondary implantation of implantable collamer lens (ICL) for correction of anisometropic hyperopia in a 3-year-old pseudophakic child. The ICL implantation was considered in our patient due to parental noncompliance for contact lens and spectacles use for one year. In terms of efficacy, the preoperative refractive error of +7.00-1.75 diopter (D) reduced to +1.00-1.75 D. The uncorrected distance visual acuity (UDVA) significantly improved from 20/400 (preoperatively) to 20/50 (postoperatively). In terms of safety, after an uneventful implantation surgery, the ICL was well tolerated, and remained well centered, with no serious postoperative complications encountered over a 22-month follow-up.


Radioimmunoassay of 2-hydroxyestrone.
Under the protection of ascorbic acid a 2-hydroxyestrone bovine serum albumin conjugate was prepared containing intact 2-hydroxyestrone as determined by gas chromatographymass spectometry. Using this antigen highely specific antibodies were raised in rabbits. Cross-reactivity for 2-hydroxyestradiol and 2-hydroxyestriol was 26 and 4.5%, respectively. An assay procedure of 2-hydroxyestrone in human plasma is described. Using special precautions the assay allows the determination of 2-hydroxyestrone in plasma samples of women (50-95 pg/ml), pregnant women (105-220 pg/ml), men (45-65 pg/ml) and children(20-40 pg/ml).


Phylogenetic relationships and taxonomic position of genus Hyperacrius (Rodentia: Arvicolinae) from Kashmir based on evidences from analysis of mitochondrial genome and study of skull morphology.
In this article, we present the nearly complete mitochondrial genome of the Subalpine Kashmir vole Hyperacrius fertilis (Arvicolinae, Cricetidae, Rodentia), assembled using data from Illumina next-generation sequencing (NGS) of the DNA from a century-old museum specimen. De novo assembly consisted of 16,341 bp and included all mitogenome protein-coding genes as well as 12S and 16S RNAs, tRNAs and D-loop. Using the alignment of protein-coding genes of 14 previously published Arvicolini tribe mitogenomes, seven Clethrionomyini mitogenomes, and also Ondatra and Dicrostonyx outgroups, we conducted phylogenetic reconstructions based on a dataset of 13 protein-coding genes (PCGs) under maximum likelihood and Bayesian inference. Phylogenetic analyses robustly supported the phylogenetic position of this species within the tribe Arvicolini. Among the Arvicolini, Hyperacrius represents one of the early-diverged lineages. This result of phylogenetic analysis altered the conventional view on phylogenetic relatedness between Hyperacrius and Alticola and prompted the revision of morphological characters underlying the former assumption. Morphological analysis performed here confirmed molecular data and provided additional evidence for taxonomic replacement of the genus Hyperacrius from the tribe Clethrionomyini to the tribe Arvicolini.


Intraoperative monitoring of brainstem auditory evoked potentials following emergency evacuation of a cerebellar vascular malformation.
This case report highlights the use and value of monitoring the auditory brainstem response during emergency neurosurgery. The prompt on-line changes in the auditory brainstem response after evacuation of a cerebellar arteriovenous malformation provided objective evidence of improved brainstem function, which aided in the management of this patient's disorder.


Delineating and understanding cerebellar neuroprotective pathways: potential implication for protecting the cortex.
The cerebellum is a brain region that is resistant to many of the neurodegenerative disorders such as stroke and Alzheimer's disease. In contrast, the neocortex (cerebrum, cerebral cortex) is vulnerable to these disorders. While there may be many reasons for the differences in vulnerability to acute and chronic neurodegenerative disorders, the cerebellum appears to be equipped with the tools necessary to protect itself against these types of insults. Over the last century, evidence has accumulated to suggest that the cerebellum is also involved in memory and higher cognitive function. We have discovered that intrinsic survival pathways exist in cerebellar granule cells that are regulated by low level stimulation of N-methyl-d-aspartate (NMDA) receptors. Activation of NMDA receptors protects vulnerable neurons against glutamate-mediated excitotoxicity acting on NMDA receptors. This report focuses on how modulation of neuronal survival by NMDA receptors through a brain-derived neurotrophic factor (BDNF)-mediated pathway may be incorporated into a network of cerebellar function, particularly in light of recent findings suggesting that the cerebellum plays a vital role in learning, memory, fear conditioning, and cognitive processing.


[Characteristics of perinatal visceral lesions caused by chlamydia trachomatis].
Twenty-three autoptic cases of perinatal chlamydiasis were analyzed. Its etiology was verified by immunofluorescence technique using monoclonal antibodies. The morphological characteristics of visceral lesions are given. Data on the possible routes of infection and evidence for the development of generalized chlamydiasis are presented. The kidney may be suggested to be the site of pathogen persistence.


A retrospective study of papillary thyroid carcinoma: Hashimoto's thyroiditis as a protective biomarker for lymph node metastasis.
There is approximately 10%-50% of papillary thyroid carcinoma (PTC) patients with Hashimoto's thyroiditis (HT). In this research, we sought to better understand the role of HT in PTC progression as well as lymph node metastasis. It is a retrospective and cross-sectional study, and 4131 PTC patients who underwent thyroidectomy were finally enrolled. Chi-square test, univariate and multivariate logistic regression analyses were employed to evaluate both the risk factors and the critical roles of HT during PTC metastasis. In this cohort, 1555 patients (37.6%) were diagnosed with HT. According to multivariate analysis, male sex, high levels of TG and TPOAb, tumor extrathyroidal extension, maximum diameter >1 cm, and multifocality were independent risk factors for both central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). In addition, age <55 years and smoking were risk factors for CLNM, while CLNM was one of the risk factors for LLNM. Furthermore, HT was suggested a valuable protective factor for both CLNM and LLNM. In patients with HT, the total number of central lymph nodes was higher, while the positive rate was lower. Compared with those without HT, age and sex did not predict CLNM and LLNM in patients with HT. HT is considered a protective factor for both CLNM and LLNM in PTC. For patients with HT, surgeons should pay more attention to the preservation of parathyroid gland and the protection of recurrent laryngeal nerve due to less lymph node metastasis. Otherwise, radical operation is highly recommended.


Low Affinity and Slow Na+ Binding Precedes High Affinity Aspartate Binding in the Secondary-active Transporter GltPh.
GltPh from Pyrococcus horikoshii is a homotrimeric Na(+)-coupled aspartate transporter. It belongs to the widespread family of glutamate transporters, which also includes the mammalian excitatory amino acid transporters that take up the neurotransmitter glutamate. Each protomer in GltPh consists of a trimerization domain involved in subunit interactions and a transport domain containing the substrate binding site. Here, we have studied the dynamics of Na(+) and aspartate binding to GltPh. Tryptophan fluorescence measurements on the fully active single tryptophan mutant F273W revealed that Na(+) binds with low affinity to the apoprotein (Kd 120 mm), with a particularly low kon value (5.1 m(-1)s(-1)). At least two sodium ions bind before aspartate. The binding of Na(+) requires a very high activation energy (Ea 106.8 kJ mol(-1)) and consequently has a large Q10 value of 4.5, indicative of substantial conformational changes before or after the initial binding event. The apparent affinity for aspartate binding depended on the Na(+) concentration present. Binding of aspartate was not observed in the absence of Na(+), whereas in the presence of high Na(+) concentrations (above the Kd for Na(+)) the dissociation constants for aspartate were in the nanomolar range, and the aspartate binding was fast (kon of 1.4 × 10(5) m(-1)s(-1)), with low Ea and Q10 values (42.6 kJ mol(-1) and 1.8, respectively). We conclude that Na(+) binding is most likely the rate-limiting step for substrate binding.


Effect of Maternal Subclinical Hypothyroidism on Congenital Hypothyroidism Screening Results: A Retrospective Cohort Study.
This study aimed to evaluate the results of congenital hypothyroidism screening (CHS) in neonates born to women with subclinical hypothyroidism (SHT) during pregnancy and to identify maternal and neonatal characteristics associated with recall rate in CHS. This retrospective cohort study included nonrefugee pregnant women and newborn pairs who underwent thyroid function tests during prenatal follow-up between 2014 and 2017 and had neonatal CHS records. The women were evaluated overall and divided into euthyroidism (ET) and SHT groups according to their thyroid function tests. The groups were compared in terms of CHS results. Neonates with thyroid-stimulating hormone (TSH) levels <5.5 mIU/L were considered "normal," while those with values ≥5.5 mIU/L were "recall." The antenatal thyroid function data of a total of 22,383 pregnant women were analyzed. Of these, 71.6% were ET and 16.3% were diagnosed as SHT. Overall, the recall rate accounted for 5.34% of all CHS results and the recall rate was higher in the SHT group (7.10%) compared with the ET group (5.54%; p = 0.001). Being low birth weight (LBW) or large for gestation age (LGA), maternal TSH above the 97.5th percentile, and cesarean delivery increased the risk of recall in CHS (p ˂ 0.05). The recall rate was higher among the neonates of mothers with SHT. Being LBW or LGA, maternal TSH above the 97.5th percentile and cesarean delivery increased the risk of recall in CHS. · SHT is the most common form of hypothyroidism in pregnancy.. · TSH elevation is higher among the neonates of mothers with SHT.. · Being LBW or LGA, and cesarean delivery also increase the risk of TSH elevation in infants..


Pseudoaneurysm detection with Tc-99m-labeled red blood cells.
A technique for the noninvasive diagnosis of pseudoaneurysms is described. This method employs in vivo labeling of red blood cells with Tc-99m to allow better delineation of the vascular anatomy than standard radionuclide angiography. Four cases are illustrated.


Evolutionary diversification of the BetaM interactome acquired through co-option of the ATP1B4 gene in placental mammals.
ATP1B4 genes represent a rare instance of orthologous vertebrate gene co-option that radically changed properties of the encoded BetaM proteins, which function as Na,K-ATPase subunits in lower vertebrates and birds. Eutherian BetaM has lost its ancestral function and became a muscle-specific resident of the inner nuclear membrane. Our earlier work implicated BetaM in regulation of gene expression through direct interaction with the transcriptional co-regulator SKIP. To gain insight into evolution of BetaM interactome we performed expanded screening of eutherian and avian cDNA libraries using yeast-two-hybrid and split-ubiquitin systems. The inventory of identified BetaM interactors includes lamina-associated protein LAP-1, myocyte nuclear envelope protein Syne1, BetaM itself, heme oxidases HMOX1 and HMOX2; transcription factor LZIP/CREB3, ERGIC3, PHF3, reticulocalbin-3, and β-sarcoglycan. No new interactions were found for chicken BetaM and human Na,K-ATPase β1, β2 and β3 isoforms, indicating the uniqueness of eutherian BetaM interactome. Analysis of truncated forms of BetaM indicates that residues 72-98 adjacent to the membrane in nucleoplasmic domain are important for the interaction with SKIP. These findings demonstrate that evolutionary alterations in structural and functional properties of eutherian BetaM proteins are associated with the increase in its interactome complexity.


Histogram-based analysis of diffusion-weighted imaging for predicting aggressiveness in papillary thyroid carcinoma.
To assess the potential of apparent diffusion coefficient (ADC) map in predicting aggressiveness of papillary thyroid carcinoma (PTC) based on whole-tumor histogram-based analysis. A total of 88 patients with PTC confirmed by pathology, who underwent neck magnetic resonance imaging, were enrolled in this retrospective study. Whole-lesion histogram features were extracted from ADC maps and compared between the aggressive and non-aggressive groups. Multivariable logistic regression analysis was performed for identifying independent predictive factors. Receiver operating characteristic curve analysis was used to evaluate the performances of significant factors, and an optimal predictive model for aggressiveness of PTC was developed. The aggressive and non-aggressive groups comprised 67 (mean age, 44.03 ± 13.99 years) and 21 (mean age, 43.86 ± 12.16 years) patients, respectively. Five histogram features were included into the final predictive model. ADC_firstorder_TotalEnergy had the best performance (area under the curve [AUC] = 0.77). The final combined model showed an optimal performance, with AUC and accuracy of 0.88 and 0.75, respectively. Whole-lesion histogram analysis based on ADC maps could be utilized for evaluating aggressiveness in PTC.


Ultralong-Circulating and Self-Targeting "Watson-Crick A = T"-Inspired Supramolecular Nanotheranostics for NIR-II Imaging-Guided Photochemotherapy.
A carrier-free theranostic nanodrug directly coassembled using a NIR probe and a chemotherapeutic drug is a promising alternative for cancer theranostics. Nevertheless, this nanodrug still faces the limitations of short blood circulation and inefficient tumor accumulation/tumoral cellular uptake in vivo. Meanwhile, most exogenous targeting ligands and poly(ethylene glycol) have no therapeutic effect. Herein, we designed an ultralong-circulating and self-targeting nanodrug by an ordered supramolecular coassembly of indocyanine green (ICG), methotrexate (MTX, chemotherapeutic drug and cancer-cell-specific ligand), and clofarabine (CA). Notably, CA, as a surfactant-like chemotherapeutic drug, was introduced into the initial ICG-MTX coassembly by "Watson-Crick A = T-inspired" hydrogen-bond-driven sequential assembly with MTX. This carrier-free theranostic nanodrug with exceptionally high drug payload (100 wt %) not only showed superior serum stabilities but also displayed ultralong blood circulation (>7 days), enabling efficient accumulation at tumor sites. Moreover, our nanodrugs could be self-recognized by cancer cells and release the drugs on demand through lysosomal acidity and external laser stimulus. Under NIR-II imaging guidance, high-efficiency tumor ablation via synergistic photothermal-chemotherapy could be achieved in one treatment cycle while preventing the tumor recurrence. Our ultralong-circulating and self-recognizing carrier-free theranostic nanodrug based on the "drug-delivering-drug" strategy might have the potential for clinical theranostic application.


Out of School and Into Distress: Families of Young Adults with Intellectual and Developmental Disabilities in Transition.
The transition period out of the educational system can be a source of stress for parents of young adults with intellectual and developmental disabilities, as families lose the support and respite offered by schools. Using a before and after design nested within a 24-month follow-up study of parents seeking adult developmental services for their children, parents' perception of distress was measured using the Brief Family Distress Scale (Journal of Child and Family Studies, 20, 2011, 521) and their perception of helpfulness of formal supports was assessed using the Family Support Scale (Journal of Individual, Family, and Community Wellness, 1, 1984, 45). Parents reported significantly higher levels of distress after their child transitioned out of school. Employed parents and parents of a child with an autism spectrum disorder are at increased risk for distress. Families fare worse once their adult children are no longer in school, although this is not associated with a reduction in the perception of the helpfulness of formal supports.


Simultaneous determination of four designer drugs and their major metabolites by liquid chromatography-mass spectrometry.
A sensitive liquid chromatography-electrospray ionization-ion trap mass spectrometry (LC-ESI-ITMS) method was utilized for the simultaneous analysis of four designer drugs and their in vitro metabolites in rat liver microsome S9 fraction. Four designer drugs, including methcathinone (MC), 3,4-methylenedioxymethcathinone (MDMC), 3,4-methylenedioxy-pyrovalerone (MDPV) and 4'-methyl-α-pyrrolidinopropiophenone (MPPP), were individually incubated with rat liver microsome S9 fraction, and the incubation mixtures were pooled together and analyzed by LC-ESI-ITMS simultaneously. Besides four designer drugs, five of their main metabolites were identified via the analysis of protonated molecules and tandem mass spectrometry data. Meanwhile, the quantification analysis of four designer drugs in rat liver microsome S9 fraction was performed, the calibration curves showed good linearity in the range of 0.01-5.0μg/mL and the detection limits were below 0.03μg/mL with RSDs less than 5.9% and recovery ratios above 77.4%. The experimental results not only showed that these designer drugs could be easily metabolized in rat liver microsome, and also displayed the superiorities of the method including time and cost saving, high efficiency, sensitivity and selectivity. The studies in this study indicated that the approach could be applied in the determination of illicit drugs and their metabolites in medical, pharmaceutical and forensic investigations.


Policy reforms for antibiotic use claims in livestock.
Antibiotics detected in "raised without antibiotics" cattle underscore the need to ensure the integrity of labeling claims.


Integrated analyses reveal evolutionarily conserved and specific injury response genes in dorsal root ganglion.
Rodent dorsal root ganglion (DRG) is widely used for studying axonal injury. Extensive studies have explored genome-wide profiles on rodent DRGs under peripheral nerve insults. However, systematic integration and exploration of these data still be limited. Herein, we re-analyzed 21 RNA-seq datasets and presented a web-based resource (DRGProfile). We identified 53 evolutionarily conserved injury response genes, including well-known injury genes (Atf3, Npy and Gal) and less-studied transcriptional factors (Arid5a, Csrnp1, Zfp367). Notably, we identified species-preference injury response candidates (e.g. Gpr151, Lipn, Anxa10 in mice; Crisp3, Csrp3, Vip, Hamp in rats). Temporal profile analysis reveals expression patterns of genes related to pre-regenerative and regenerating states. Finally, we found a large sex difference in response to sciatic nerve injury, and identified four male-specific markers (Uty, Eif2s3y, Kdm5d, Ddx3y) expressed in DRG. Our study provides a comprehensive integrated landscape for expression change in DRG upon injury which will greatly contribute to the neuroscience community.


Quality assurance in radiation therapy: systematic evaluation of errors during the treatment execution.
A method to control the quality of the radiotherapy treatment during its execution has been developed. The method is based on a wide use of verification films in the practical routine of a centre together with a statistical analysis of the data obtained from them. The stepwise multiple regression analysis is applied in order to assess the influence, on the quality of the treatment, of a set of chosen factors with a certain clinical or technical significance. A test of the method is presented and the results are discussed.


Algorithms for the optimal identification of segment neighborhoods.
Two algorithms for the efficient identification of segment neighborhoods are presented. A segment neighborhood is a set of contiguous residues that share common features. Two procedures are developed to efficiently find estimates for the parameters of the model that describe these features and for the residues that define the boundaries of each segment neighborhood. The algorithms can accept nearly any model of segment neighborhood, and can be applied with a broad class of best fit functions including least squares and maximum likelihood. The algorithms successively identify the most important features of the sequence. The application of one of these methods to the haemagglutinin protein of influenza virus reveals a possible mechanism for conformational change through the finding of a break in a strong heptad repeat structure.


Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice.
Parkinson's Disease (PD) is a chronic and progressive neurodegenerative disease manifesting itself with tremors, muscle stiffness, bradykinesia, dementia, and depression. Mutations of mitochondrial E3 ligase, PARKIN, have been associated with juvenile PD. Previous studies have characterized muscle atrophy and motor deficits upon loss of functional Parkin in fly and rodent models. However, the mechanisms behind pathophysiology of Parkin deficient muscle remains to be elusive. Here, results suggested that knock down of Parkin significantly increases proteolytic activities in skeletal muscle cell line, the C2C12 myotubes. However, the atrogene levels increase moderately in Parkin deficient cell line. To further investigate the role of Parkin in skeletal muscle atrophy, Parkin knock out (KO) and wild type mice were subjected to 48 h starvation. After 48 h fasting, a greater reduction in skeletal muscle weights was observed in Parkin KO mice as compared to age matched wild type control, suggesting elevated proteolytic activity in the absence of Parkin. Subsequent microarray analyses revealed further enhanced expression of FOXO and ubiquitin pathway in fasted Parkin KO mice. Furthermore, a greater reduction in the expression of cytoskeleton genes was observed in Parkin KO mice following 48 h fasting. Collectively, these results suggest that Parkin deficiency exacerbates fasting-induced skeletal muscle wasting, through upregulating genes involved in catabolic activities in skeletal muscle.


Burnout as a predictor of depression: a cross-sectional study of the sociodemographic and clinical predictors of depression amongst nurses in Cameroon.
Depression is a debilitating mental health condition which affects an estimated 350 million people worldwide annually. Nurses are twice as likely to suffer from depression than professionals in other professions. This leads to a considerable loss of efficiency and productivity. We sought to determine the prevalence and predictors of depression among nurses in Cameroon. Cross-sectional analysis carried out over 6 months (January - June 2018) using nurses from public and private healthcare institutions sampled consecutively in the two English-speaking regions (North west and South west regions) of Cameroon. The nurses were handed a structured, printed, self-administered questionnaire to fill and hand in at their earliest convenience. Depression and burnout were assessed using the Patient Health Questionnaire - 9 and the Oldenburg Burnout Inventory respectively. A total of 143 nurses were recruited (mean age: 29.75 ± 6.55 years; age range: 20-55 years, 32.87% male). The overall prevalence of depression was 62.24%. Independent predictors of depression after multivariable analysis were: Number of night shifts a week (adjusted odds ratio: 1.58; p value: 0.045, 95% CI; 1.01, 2.48) and Total Oldenburg Burnout Inventory score (adjusted odds ratio: 1.21, p value: 0.001; 95% CI; 1.08, 1.35). Recreational drug use was also found to perfectly predict the outcome - depression. Depression is highly prevalent among nurses in the English-speaking regions of Cameroon. Accurate predictors could prove vital for early detection and management of affected individuals. Predictors presented herein require further investigation via multicentric nationwide studies, to obtain more generalizable results.


Associations between adolescent experiences of violence in Malawi and gender-based attitudes, internalizing, and externalizing behaviors.
Little is known about adolescent exposure to and factors associated with violence in Malawi. The aim of this research was to describe the prevalence of exposure to violence among adolescents in Malawi, and test the hypotheses that such exposures are associated with gender-based violent attitudes, and with internalizing and externalizing problems. In 2014, 561 primary school pupils were interviewed (50% girls), and logistic regression analysis was performed on gender-stratified data, adjusting for sociodemographic differences. Both girls and boys had witnessed domestic violence (28.5% & 29.6%), experienced emotional abuse at home (23.1% & 22.9%), physical abuse at home (28.1% & 30.4%), physical abuse at school (42.4% & 36.4%), and been bullied (33.8% & 39.6%). Among girls, internalized violent attitudes towards women were associated with emotional abuse at home (OR 2.1) and physical abuse at school (OR 1.7). Condoning rape was associated with physical abuse at school (OR 1.9). Bullying perpetration was associated with emotional abuse at home (OR 4.5). Depression was associated with emotional abuse at home (OR 3.8) and physical abuse at school (OR 2.4). Among boys, violent attitudes towards women and condoning rape were not associated with violence exposure. Bullying perpetration was associated with having been a victim of bullying (OR 2.9) and physical abuse at school (OR 2.7). Depression was associated with emotional abuse at home (OR 2.9), domestic violence (OR 2.4) and physical abuse at school (OR 2.5). These findings can inform programs designed to reduce violence victimization among Malawian girls, both in homes and schools.


Louis Ranvier (1835-1922): the contribution of microscopy to physiology and the renewal of French general anatomy.
The French neurohistologist Louis-Antoine Ranvier (1835-1922), somewhat neglected in classical histories of nineteenth-century studies on the nervous system, developed a personal style, traditionally referred to as a synthesis between histology and physiology. Ranvier's research was not centered on the brain. Rather, he remained attached to the intimate nature of minute structures, with a style marked by the concept of generality. Ranvier's original style and role in the development of French histology and anatomie générale are analyzed, and their significance evaluated. Ranvier is reassessed as a prominent figure and as the leader in the renewal of the French anatomy.


Genetically engineered livestock: closer than we think?
The potential of biotechnology to benefit production agriculture has long been speculated. Whereas many transgenic crops have been produced and commercialized, there has yet to be any implementation of genetically engineered livestock. A recent publication by Wall et al. represents one of the first reports to bring the potential of genetic engineering closer to realization by improving disease resistance in dairy cattle: a practical advantage to both the producer and animal.


Chaperone and foldase coexpression in the baculovirus-insect cell expression system.
The BEVS has become widely utilized for production of recombinant proteins. However, protein aggregation and inefficient processing often limit yields, especially for secreted and membrane proteins. Since many proteins of pharmaceutical interest require similar posttranslational processing steps, engineering the folding, assembly, and secretion pathway may enhance the production of a wide variety of valuable complex proteins. Efforts should be undertaken to coexpress the relevant chaperones or foldases at low levels in concert with the final product to ensure the ideal folding and assembly environment. In the future, expression of oligosaccharide modifying enzymes and secretion factors may further improve secretion rates of assembled proteins and provide heterologous proteins with altered glycoforms. Also significant is the use of BEVS as an in vivo eucaryotic laboratory to study the fundamental roles of differnt chaperones, foldases, and secretion factors. The coexpression of chaperones and foldases will complement other approaches such as the development of alternative insect cell lines, promoters, and signal peptides to optimize the baculovirus-insect cell expression system for generating high yields of valuable proteins.


Life span extension by dietary restriction is reduced but not abolished by loss of both SIR2 and HST2 in Podospora anserina.
Dietary restriction (DR) extends life span of many organisms, from yeast to mammals. The question of whether or not the SIR2 protein functions to mediate life span extension in response to DR remains debated. In this paper, we studied the relationship between SIR2 and DR in the filamentous fungus Podospora anserina. We show that the loss of PaSir2, PaHst2 or PaPnc1 does not alter life span under standard conditions. PaHst2 is the closest paralog of PaSir2 and the ortholog of yeast HST2 and PaPnc1 is the ortholog of the yeast PNC1 which encodes a nicotinamidase that deaminates nicotinamide, a natural inhibitor of SIR2. As observed for other organisms, overexpression of PaSir2 weakly increases life span under standard condition. Under DR conditions, deletion of the PaSir2 or PaHst2 genes induce a significant reduction in life span extension, while the double mutant strongly reduces life span extension. However, a clear response to DR subsists in the double mutant, demonstrating that DR acts through a SIR2/HST2 independent pathway.


Statistical challenges in the analysis of dynamic traits: implications for pharmacogenomic clinics.
Analysis of dynamic traits is statistically challenging for several reasons. Since most of the dynamic traits result in irregular sparse longitudinal measurements, a unified approach for jointly modeling the mean trajectories and the underlying covariance structure is essential. When the traits are bivariate or multivariate in nature, modeling the covariance structure is really challenging. For the pharmacogenomic clinics, it is extremely important to have a comprehensive study of the whole biological system. In other words, if the traits under consideration result in some events (e.g., death, disease), then a joint analysis is required for the observed dynamic traits and the event-time. In statistics, there is a vast literature on such joint modeling using parametric, nonparametric and semiparametric approaches. In this article, we will discuss different aspects of modeling the longitudinal traits, their limitations and importance to pharmacogenomic clinics.


Drug-oxidizing and conjugating non-cytochrome P450 (non-P450) enzymes in cynomolgus monkeys and common marmosets as preclinical models for humans.
Many drug oxidations and conjugations are mediated by a variety of cytochromes P450 (P450) and non-P450 enzymes in humans and non-human primates. These non-P450 enzymes include aldehyde oxidases (AOX), carboxylesterases (CES), flavin-containing monooxygenases (FMO), glutathione S-transferases (GST), arylamine N-acetyltransferases (NAT),sulfotransferases (SULT), and uridine 5'-diphospho-glucuronosyltransferases (UGT) and their substrates include both endobiotics and xenobiotics. Cynomolgus macaques (Macaca fascicularis, an Old-World monkey) are widely used in preclinical studies because of their genetic and physiological similarities to humans. However, many reports have indicated the usefulness of common marmosets (Callithrix jacchus, a New World monkey) as an alternative non-human primate model. Although knowledge of the drug-metabolizing properties of non-P450 enzymes in non-human primates is relatively limited, new research has started to provide an insight into the molecular characteristics of these enzymes in cynomolgus macaques and common marmosets. This mini-review provides collective information on the isoforms of non-P450 enzymes AOX, CES, FMO, GST, NAT, SULT, and UGT and their enzymatic profiles in cynomolgus macaques and common marmosets. In general, these non-P450 cynomolgus macaque and marmoset enzymes have high sequence identities and similar substrate recognitions to their human counterparts. However, these enzymes also exhibit some limited differences in function between species, just as P450 enzymes do, possibly due to small structural differences in amino acid residues. The findings summarized here provide a foundation for understanding the molecular mechanisms of polymorphic non-P450 enzymes and should contribute to the successful application of non-human primates as model animals for humans.


Promising roles of Zingiber officinale roscoe, Curcuma longa L., and Momordica charantia L. as immunity modulators against COVID-19: A bibliometric analysis.
Zingiber officinale, Curcuma longa, and Momordica charantia are medicinal plants that are commonly used in the form of herbal tea, which is formulated to strengthen the immune system, especially against COVID-19 infection. Excellent antioxidant, anti-inflammatory, and immunostimulatory properties have been reported for their bioactive compounds, which have been shown to aid in stimulating immune systems as well as lowering the risk of severe COVID-19 such as lung injury. Yet, no bibliometric study on the subject is available. Hence, the purpose of this study is to quantitatively examine the existing articles related to the therapeutic potential of these three herbs, as well as their mechanisms of action in combating the SARS-CoV-2 virus. A total of 121 papers were retrieved from Scopus database up to 14th March 2023. The bibliometric analysis was conducted using VOSviewer software. Based on the literature search, Z. officinale was the most researched plant. India appeared as the most prolific country, with the highest number of articles contributed by two authors from India (Rathi, R. and Gayatri Devi, R.). In terms of keywords, the plants were associated with immune modulation, management of symptoms, antioxidant, anti-inflammatory and antiviral activities. Several important bioactive compounds were responsible for these effects such as gingerol, paradol, shogaol, curcumin, calebin A, momordicoside, karaviloside and cucurbitadienol. These compounds were hypothesized to prevent and cure COVID-19 by regulating inflammatory response, downregulating oxidative stress and modulating immunostimulatory activity. This review paper therefore supports the potential of Z. officinale, C. longa, and M. charantia to be formulated as a herbal blend for treating and preventing COVID-19 infection.


Injectable in situ forming thermo-responsive graphene based hydrogels for cancer chemo-photothermal therapy and NIR light-enhanced antibacterial applications.
Functionalized graphene oxide (GO) and reduced GO (rGO) based nanomaterials hold a great potential for cancer photothermal therapy. However, their systemic administration has been associated with an accelerated blood clearance and/or with suboptimal tumor uptake. To address these limitations, the local delivery of GO/rGO to the tumor site by 3D matrices arises as a promising strategy. In this work, injectable chitosan-agarose in situ forming thermo-responsive hydrogels incorporating GO (thermogel-GO) or rGO (thermogel-rGO) were prepared for the first time. The hydrogels displayed suitable injectability and gelation time, as well as good physicochemical properties and cytocompatibility. When irradiated with near infrared (NIR) light, the thermogel-rGO produced a 3.8-times higher temperature increase than thermogel-GO, thus decreasing breast cancer cells' viability to 60%. By incorporating an optimized molar ratio of the Doxorubicin:Ibuprofen combination on thermogel-rGO, this formulation mediated a chemo-photothermal effect that further diminished cancer cells' viability to 34%. In addition, the hydrogels' antibacterial activity was further enhanced upon NIR laser irradiation, which is an important feature considering the possible risk of infection at the site of administration. Overall, thermogel-rGO is a promising injectable in situ forming hydrogel for combinatorial chemo-photothermal therapy of breast cancer cells and NIR light enhanced antibacterial applications.


IGF-I concentrations are positively associated with carotid artery atherosclerosis in women.
Alterations in the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis are associated with increased cardiovascular morbidity and mortality, but previous studies have yielded conflicting results. In addition, the T1169A polymorphism in the GH1 gene has been associated with IGF-I levels. To investigate whether IGF-I concentrations and the T1169A polymorphism of the GH1 gene are associated with cardiovascular risk factors and the intima media thickness (IMT) of the carotid artery. Fasting plasma IGF-I concentrations (n=1008) were measured in a large population-based OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort. Genotype variants were determined by the restriction fragment length polymorphism method. Low IGF-I concentrations associated with several cardiovascular risk factors including age, adiposity, and high triglyceride, fasting insulin and C-reactive protein concentrations in the analysis of all subjects. In the multivariate models, however, IGF-I concentrations were positively associated with the mean IMT of women (ss=0.127, P=0.009) whereas the association in men was weaker and negative (ss=-0.088, P=0.034). The 1169A allele was associated with low low-density lipoprotein cholesterol in both sexes and with low systolic blood pressure levels in women. IGF-I concentrations were associated with several traditional cardiovascular risk factors. The observed gender difference in the association between IGF-I concentrations and carotid artery atherosclerosis warrants further study. The GH1 1169A allele may be associated with a favourable metabolic profile.


A novel regression model from RGB image data to spectroradiometric correlates optimized for tooth colored shades.
Objectives of this study were to correlate RGB data from the VITA Linearguide 3D Master and VITA Bleached Guide 3D Master shade guides with their spectroradiometric correlates through a regression model while indicating a methodology for validation of accuracy of digital imaging systems. Additional objectives were to provide summary RGB data and to determine a relationship between lightness and RGB values for these shade guides. Radiant energy measurements and images were taken with a Canon Rebel T3i and Macro Ring Lite MR-14EX for each shade tab. RGB data was extracted using Image J and compared with spectroradiometric measurements. Regression models relating the RGB data to spectroradiometric counterparts in CIE XYZ and absolute reflectance were developed using SAS 9.3. Image data was statistically analyzed to determine a relationship between RGB values and lightness. Regression models with R(2) values greater than 0.99 for RGB to XYZ and greater than 0.95 for RGB to absolute reflectance were developed. Summary RGB data for the shade guides including Pearson correlation coefficients ranging between -0.92 and -0.97 for RGB related to lightness was determined. A relationship between RGB and lightness for the shade guides was found. Regression models were developed that allow tooth color information to be translated from digital images to accurate shade tab correlates for color matching purposes in dentistry. This allows for optimal color accuracy when using digital imaging to translate color information and provides a method of validating digital imaging systems for color accuracy.


Efficient intracellular multiplication of Legionella pneumophila in human monocytes requires functional host cell L-type calcium channels.
The infectious agent of Legionnaires' disease, Legionella pneumophila, multiplies intracellularly in a variety of eukaryotic cells. Genistein, a tyrosine kinase inhibitor, has been shown to block intracellular replication of L. pneumophila without harming the infected host cell. The present study has been performed to investigate the underlying mechanism. We demonstrate that inhibition of intracellular bacterial growth by genistein is not mediated by its protein tyrosine kinase-modulating effect but by inhibition of L-type calcium channels of the infected host cell.


The effects of carbon pricing instruments on carbon emission reduction in China's refining industry: an evolutionary game between heterogeneous refineries.
Carbon emissions from the refining industry are receiving increasing national attention. In view of long-term sustainable development, a carbon pricing mechanism oriented to carbon emission reduction needs to be developed. Currently, the two most common carbon pricing instruments are emission trading system and carbon tax. Therefore, it is important to study the carbon emission problems in the refining industry under emission trading system or carbon tax. Based on the current situation of China's refining industry, this paper constructs an evolutionary game model for backward and advanced refineries to explore which instrument is more effectively applied in the refining industry and identify the effective factors that can promote carbon emission reduction in refineries. According to the numerical results, if the heterogeneity of enterprises is small, the government's implementation of an emission trading system is the most effective measure, while carbon tax can only ensure that the equilibrium strategy solution is (1,1) when the tax rate is high. If the heterogeneity is large, the carbon tax policy will not have any effect, indicating that government implementation of an emission trading system is more effective than the carbon tax. In addition, there is a positive relationship between carbon price, carbon tax, and refineries' agreement to carbon emission reduction. Finally, consumers' preference for low-carbon products, R&D investment level, and R&D spillover effect have nothing to do with carbon emission reduction. Only by reducing refinery heterogeneity and improving the R&D efficiency of backward refineries can all enterprises agree to carbon emission reduction.


[Transcultural clinical approach at all ages].
The Maison de Solenn at Cochin hospital in Paris provides transcultural care to a local migrant population. The transcultural approach consists in taking into account the cultural dimension in care and favours, through a specific technique, the sharing of cultural representations between professionals and families. The therapists can move around the hospital to provide advice as and when required, notably to facilitate care and compliance and to ensure there are no misunderstandings regarding treatments. In some situations, we recommend a transcultural consultation which consists in forming a group of several therapists from diverse professional and cultural backgrounds, to discuss a complex situation with the patient and their family.


Milestones on a Shoestring: A Cost-Effective, Semi-automated Implementation of the New ACGME Requirements for Radiology.
The advent of the ACGME's Next Accreditation System represents a significant new challenge for residencies and fellowships, owing to its requirements for more complex and detailed information. We developed a system of online assessment tools to provide comprehensive coverage of the twelve ACGME Milestones and digitized them using freely available cloud-based productivity tools. These tools include a combination of point-of-care procedural assessments, electronic quizzes, online modules, and other data entry forms. Using free statistical analytic tools, we also developed an automated system for management, processing, and data reporting. After one year of use, our Milestones project has resulted in the submission of over 20,000 individual data points. The use of automated statistical methods to generate resident-specific profiles has allowed for dynamic reports of individual residents' progress. These profiles both summarize data and also allow program directors access to more granular information as needed. Informatics-driven strategies for data assessment and processing represent feasible solutions to Milestones assessment and analysis, reducing the potential administrative burden for program directors, residents, and staff.


Viabahn-assisted sutureless anastomosis (VASA) repair of a complex internal carotid artery aneurysm.
Extracranial carotid artery aneurysms (CAAs) are extremely rare and often require surgical intervention to avoid complications such as local compression symptoms and thrombo-embolization. We present the case of a 63-year-old man with a history of hypertension, meningioma, and an incidental finding of a right saccular internal carotid artery aneurysm at the base of the skull. He underwent open surgical repair; nonetheless, end-to-end anastomosis was not feasible. As bailout, the internal carotid artery was successfully reconstructed with a novel Viabahn-assisted sutureless anastomosis technique (GORE, Viabahn). Postoperative clinical assessment revealed no complications, postoperative computed tomography angiography revealed a patent reconstruction, and the patient was discharged home uneventfully with 1-year clinical and computed tomography angiography follow-up without remarks. Hybrid procedure is a viable option for technically challenging carotid anastomoses near the skull base.


Dental caries according to CAST among Zambian adolescents; pattern, socio-demographic and behavioral correlates.
Dental Caries affect more than half of children and adolescents globally and more so in Africa. Most caries studies in Africa are based on DMFT index which does not assess early carious lesions making early prevention and minimal invasive treatment impossible. This study therefore aimed at determining pattern, socio-demographic and behavioral correlates of dental caries according to Caries Assessment and Treatment Spectrum (CAST). Cross-sectional study involving secondary school adolescents in Copperbelt province, Zambia. Socio-demographics and oral health related behaviors were assessed using a structured questionnaire while dental caries was assessed using CAST. Data were summarized as frequency distributions while cross-tabulation with Chi-squire test and adjusted multinomial logistic regression assessed strength and direction of relationship between socio-demographics, oral health behaviors and dental caries. Level of statistical significance was set at 5%. A total of 1,794 participants were enrolled 54% being females. Total frequency of adolescents with healthy teeth (CAST0-2) was 51.1%, pre-morbidity stages (CAST 3-4) was 24.7%, severe morbidity CAST (6-7) was 6.4% and mortality was 2.7%. The odds of being found with teeth at pre-morbidity stage decreased among male OR (95%CI) = 0.55 (0.44, 0.70) and younger participants OR (95%CI) = 0.77 (0.61, 0.98). Participants in high socio-economic status had lower odds of morbidity OR (95%CI) = 0.69 (0.52, 0.92) while those taking sugary foods five times or more per day had higher odds of morbidity OR (95%CI = 1.52 (1.01, 2.34). The odds of being found at mortality clinical stage of caries was lower among males OR (95% CI) = 0.53 (0.29, 0.96) and those who did not attend to a dentist in the previous year OR (95%CI) = 0.42 (0.23, 0.75), while higher odds OR (95%CI = 2.01 (1.02, 3.97) were among the high socio-economic status. The proportion of participants with teeth at pre-morbidity and morbidity were high. Socio-demographics and behavioral predictors of dental caries were sex, socio-economic status, frequency of sugary food intake per day and dental visit in the previous year.


Phenylephrine-induced cardiomyocyte injury is triggered by superoxide generation through uncoupled endothelial nitric-oxide synthase and ameliorated by 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxyindazole (DY-9836), a novel calmodulin antagonist.
The pathophysiological relevance of endothelial nitric-oxide synthase (eNOS)-induced superoxide production in cardiomyocyte injury after prolonged phenylephrine (PE) exposure remains unclear. The aims of this study were to define the mechanism of O2(*) production by uncoupled eNOS and evaluate the therapeutic potential of a novel calmodulin antagonist 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxyindazole (DY-9836) to rescue hypertrophied cardiomyocytes from PE-induced injury. In cultured rat cardiomyocytes, prolonged exposure for 96 h to PE led to translocation from membrane to cytosol of eNOS and breakdown of caveolin-3 and dystrophin. When NO and O2(*) production were monitored in PE-treated cells by 4-amino-5-methylamino-2',7'-difluorofluorescein and dihydroethidium, respectively, Ca(2+)-induced NO production elevated by 5.7-fold (p < 0.01) after 48-h PE treatment, and the basal NO concentration markedly elevated (16-fold; p < 0.01) after 96-h PE treatment. On the other hand, the O2(*) generation at 96 h was closely associated with an increased uncoupled eNOS level. Coincubation with DY-9836 (3 microM) during the last 48 h inhibited the aberrant O2(*) generation nearly completely and NO production by 72% (p < 0.01) after 96 h of PE treatment and inhibited the breakdown of caveolin-3/dystrophin in cardiomyocytes. PE-induced apoptosis assessed by TdT-mediated dUTP nick-end labeling staining was also attenuated by DY-9836 treatment. These results suggest that O2(*) generation by uncoupled eNOS probably triggers PE-induced cardiomyocyte injury. Inhibition of abnormal O2(*) and NO generation by DY-9836 treatment represents an attractive therapeutic strategy for PE/hypertrophy-induced cardiomyocyte injury.


Total tumor diameter: the neglected value in papillary thyroid microcarcinoma.
Tumor multifocality is not uncommon in papillary thyroid carcinoma (PTC), especially in micro-PTC. However, assessing the size of the largest tumor may underestimate effect of additional foci. We aimed to investigate the effect of total tumor diameter (TTD) on clinicopathological features of micro-PTC. Data from 442 patients who underwent thyroidectomy with cervical lymph node dissection for PTC were retrospectively analyzed. Patients were classified into subgroups according to multifocality and TTD. The relationships of clinicopathological features among these groups were analyzed. Multifocality was observed in 119 patients (26.9%). TTD > 1 cm and presence of extrathyroidal extension (ETE) were significantly higher in multifocal tumors compared to unifocal tumor (P < 0.001, P = 0.016, respectively). When comparing multifocal micro-PTC with TTD > 1 cm to those with unifocal micro-PTC or multifocal micro-PTC with TTD ≤ 1 cm, the proportions of cases with ETE, central lymph node metastasis (CLNM), and lateral lymph node metastasis (LLNM) were significantly higher (all P < 0.05). There was no significant difference in terms of these parameters between multifocal micro-PTC with TTD > 1 cm and macro-PTC or multifocal macro-PTC. The risk of CLNM was 2.056 (P = 0.044) times higher in multifocal micro-PTC with TTD > 1 cm than in unifocal micro-PTC. For multifocal micro-PTC, TTD can better assess the aggressiveness of the tumor. Multifocal micro-PTC with TTD > 1 cm was more aggressive than unifocal micro-PTC or multifocal micro-PTC with TTD ≤ 1 cm.


A method for raytracing through schematic eyes with off-axis components.
A linear algebraic method for tracing skew rays through aspheric surfaces is described. The advantage of this method is that the refracting surfaces can be translated and rotated with respect to each other. The method is used to investigate the optical factors affecting the location of Purkinje images.


From necessity to sufficiency in memory research: when sleep helps to understand wake experiences.
Memory is the ability to adapt our behavior by using the stored information, previously encoded. The first investigations of the neuronal bases of the memory trace concerned its properties (location, cellular and molecular mechanisms, among others). However, to understand how this is achieved at the scale of neurons, we must provide evidence about the necessity of a neuronal subpopulation to support the memory trace, but also its sufficiency. Here, we will present past and recent studies that provide information about the neuronal nature of memories. We will show that research on sleep, when cells assembly supposedly carrying information from the past are replayed, could also provide valuable information about the memory processes at stake during wake.


Implication of JNK pathway on tau pathology and cognitive decline in a senescence-accelerated mouse model.
The senescence accelerated mouse-prone 8 (SAMP8) strain of mice is an experimental model of accelerated senescence that also shares several pathological features with Alzheimer's disease. Among them, cognitive impairments and abnormal hyperphosphorylation of tau are ameliorated by the phosphodiesterase 5 inhibitor sildenafil, possibly through the modulation of Cdk5/p25 and Akt/GSK-3β pathways. Here we studied the implication of protein phosphatase 2A (PP2A) and c-Jun N-terminal kinase (JNK) in the therapeutic effects of sildenafil. Results demonstrated that there were no differences in hippocampal PP2A protein levels or activity (measured by its inactive isoform phopho-PP2A Y307) when we compared 6-month old SAMP8 mice and age-matched control, SAMR1 mice, treated with saline or sildenafil (7.5mg/kg i.p. for 4 weeks). However, this same treatment of sildenafil, that had been shown to reverse the cognitive impairment and tau hyperphosphorylation in this animal model, also reversed the increased levels of activated JNK (p-JNK) found in the hippocampus of SAMP8 mice. Moreover, the administration of the JNK inhibitor, D-JNKI-1 (0.2mg/kg i.p. for 3 weeks) also ameliorated the cognitive deficits shown by SAMP8 mice in the Morris water maze and decreased hippocampal levels of phospho-c-Jun(Ser73). When phosphorylated tau (AT8 epitope) was analyzed a significant reduction was observed in the hippocampus of D-JNKI-1 treated SAMP8 mice, providing a plausible explanation for the attenuation of cognitive decline shown by these animals. These findings suggest the involvement of the JNK pathway on tau pathology and cognitive deficits shown by 6-month old SAMP8 mice. They also point to the modulation of this kinase to be among the mechanisms responsible for the beneficial effects shown by sildenafil.


Magnetic "Molecular Oligomers" Based on Decametallic Supertetrahedra: A Giant Mn49 Cuboctahedron and its Mn25Na4 Fragment.
Two nanosized Mn49 and Mn25Na4 clusters based on analogues of the high-spin (S=22) [Mn(III)6Mn(II)4(μ4-O)4](18+) supertetrahedral core are reported. Mn49 and Mn25Na4 complexes consist of eight and four decametallic supertetrahedral subunits, respectively, display high virtual symmetry (O(h)), and are unique examples of clusters based on a large number of tightly linked high nuclearity magnetic units. The complexes also have large spin ground-state values (Mn49: S=61/2; Mn25Na4: S=51/2) with the Mn49 cluster displaying single-molecule magnet (SMM) behavior and being the second largest reported homometallic SMM.


Effect of insulin on ketone body clearance studied by a ketone body "clamp" technique in normal man.
The effect of elevated plasma insulin concentration (55 +/- 2 mU/l) on peripheral clearance and production of total ketone bodies was determined using 3-14C-acetoacetate tracer infusions. Nine normal subjects were studied twice, once during insulin infusion (20 mU.m-2.min-1), once during basal plasma insulin concentrations (controls). Blood total ketone body concentrations (sum of acetone, acetoacetate and beta-hydroxybutyrate) were maintained in both studies at 2 mmol/l by feedback-controlled sodium acetoacetate infusions. The coefficient of variation of total ketone body concentrations during the two clamp studies was 10 and 11% respectively. The sodium acetoacetate infusion rate required during the clamp was 55 +/- 4% higher during hyperinsulinaemia than in controls (p less than 0.005). This was due to increased total ketone body clearance (8.4 +/- 0.7 vs 6.7 +/- 0.4 ml.kg-1.min-1, p less than 0.015), and to enhanced suppression of ketone body production (p less than 0.01). Hyperketonaemia alone decreased ketone body production by 42% and diminished ketone body clearance by 46%, the former being enhanced, the latter being in part antagonised by insulin. Since the plasma insulin concentrations were within those observed in patients treated for diabetic ketoacidosis, the data suggest that the antiketotic effect of insulin therapy results in part from an increase in peripheral ketone body disposal.


Study of the heterologous gene expression characteristics of a new clone of a cell line derived from Papilio xuthus and its serum-free adaptation.
The baculovirus expression vector system using insect cells as a bioreactor has been used for in vitro expression of recombinant proteins and plays an important role in the fields of biology, agronomy, and medicine. Screening suitable host cell lines is an important part of the construction of insect cell baculovirus expression systems. In previous research, we used a single-cell cloning process with the Papilio xuthus cell line RIRI-PX1 and obtained the monoclonal cell line RIRI-PX1-C31. In this study, we compared the basic biological and recombinant protein expression characteristics of RIRI-PX1-C31 and its parent cell line RIRI-PX1 and found that the expression of recombinant β-galactosidase in RIRI-PX1-C31 was significantly higher than that in the parental cell line. Further serum-free adaptation studies confirmed that RIRI-PX1-C31 can adapt to the growth environment of Express Five Serum-free medium and that its expression level of recombinant β-galactosidase was significantly higher than that before adaptation.


What do dads want? Treatment preferences for paternal postpartum depression.
Postpartum depression (PPD) is prevalent, occurring in 8 to 13% of new fathers. Identifying effective and acceptable treatments for paternal PPD is important to prevent negative family outcomes. Participation in a patient preferred treatment for depression increases treatment adherence and effectiveness. Thus, developing and delivering interventions that are preferred by the target population is an important aspect of successful treatment. The current study investigated treatment preferences for paternal PPD. Men (N=140) who were within the first year postpartum were recruited from low-risk maternity clinics, baby shows, and partner referrals. Participants completed a 20-minute online survey that included three expert validated treatment descriptions for depression and a series of questionnaires. Participants reported preferring individual and couple psychotherapy to pharmacotherapy for treatment of PPD. Men perceived both individual and couple psychotherapy as being more credible and reported more favourable personal reactions towards them when compared to pharmacotherapy. Participants were not required to meet diagnostic criteria for depression. The majority of participants were asked to respond to a hypothetical scenario of what they would do if faced with PPD. These findings suggest that fathers prefer psychological interventions over pharmacotherapy for treatment of PPD. Future research should investigate efficacious treatment options for paternal PPD based on treatment preferences.


High nitrite-nitrogen stress intensity drives nitrite anaerobic oxidation to nitrate and inhibits methanogenesis.
Nitrite is an important intermediate in nitrogen metabolism. We explored the effect of nitrite-nitrogen stress intensity (NNSI) on nitrite metabolism and methanogenesis in anaerobic digestion. The results showed that the NNSI regulated microbial diversity, composition, and functions, and microbial community assembly was primarily shaped by stochastic processes. Moreover, the NNSI was negatively correlated with α-diversity and positively correlated with non-metric multi-dimensional scaling distance. Denitrification gradually increased with increasing NNSI; however, methanogenesis was gradually inhibited, which was primarily due to the inhibition of the aceticlastic methanogenesis pathway (i.e., Methanosaeta) and methylotrophic methanogenesis pathway (i.e., Candidatus_Methanofastidiosum). High NNSI (1882 ± 98.99 mg/L NO2--N) promoted nitrite anaerobic oxidation to nitrate and was favorable for dissimilatory nitrate reduction to ammonia (DNRA). We present evidence for the microbial transformation of nitrite under anaerobic conditions, with potential geochemical and evolutionary importance. As nitrogen oxides were already present on early Earth, our finding presents the possibility of a nitrogen cycle before the evolution of oxygenic photosynthesis.


A prospective study of amniotic fluid cholinesterases: comparison of quantitative and qualitative methods for the detection of open neural tube defects.
The value of quantitative and qualitative methods of cholinesterase (ChE) analysis in the detection of open neural tube defect (NTD) has been assessed in a prospective survey of 1495 mid-trimester amniotic fluids. Using a quantitative method the mean ChE values were much lower in fluids from pregnancies of normal outcome but it was not possible to discriminate these fluids completely from those associated with NTD pregnancies, particularly when the specimens were contaminated with blood. Similarly, measurement of acetylcholinesterase (AChE) activity alone by three different methods also failed to eliminate the overlap between the two groups. In contrast, polyacrylamide gel electrophoresis revealed only a single band of ChE activity in 1408 out of 1410 fluids from pregnancies with a normal outcome whilst amniotic fluids from all 60 cases of open NTD, 6 out of 7 cases of exomphalos and 3 out of 4 cases of intra-uterine death gave the characteristic second faster-running AChE band. A qualitative gel method which requires the same amount of ChE activity to be loaded from each amniotic fluid is an effective method for pre-natal diagnosis of NTDs.


Subcellular localization of the inositol 1,4,5-trisphosphate receptor, P400, in the vestibular complex and dorsal cochlear nucleus of the rat.
The subcellular localization of the inositol 1,4,5-trisphosphate receptor protein, P400, was studied in the vestibular complex, an area to which Purkinje cells project, as well as in neurons of the dorsal cochlear nucleus and in ectopic Purkinje cells of adult rat brain. The receptor was demonstrated by electron microscopical immunocytochemistry using the avidin-biotin peroxidase complex procedure, with the monoclonal antibody 4C11 raised against mouse cerebellar inositol 1,4,5-trisphosphate receptor protein. Immunoreactivity was found in preterminal fibres and terminal boutons in the nuclei of the vestibular complex, generally associated with the subsurface systems and stacks or fragments of smooth endoplasmic reticulum. Ectopic Purkinje cells and cartwheel cells of the dorsal cochlear nucleus also displayed immunoreactivity, but this was much less intense in the latter. The results of the present study suggest that this receptor protein, involved in the release of Ca2+, is located in sites that enable it to influence the synthesis, transport and release of neurotransmitters.


Toxicity and cosmetic outcomes after treatment with a novel form of breast IORT.
Intraoperative radiation therapy (IORT), a form of accelerated partial breast irradiation (APBI), is an appealing alternative to postoperative whole breast irradiation for early-stage breast cancer. The purpose of this study was to examine the toxicity and cosmetic outcomes of patients treated with a novel form of breast IORT (precision breast IORT; PB-IORT), that delivers a targeted, higher dose of radiation than conventional IORT. The first 204 patients treated with PB-IORT in a Phase II clinical trial (NCT02400658) with 12 months of followup were included. Trial inclusion criteria were age ≥45 years, invasive or in situ breast cancer, tumor size ≤3 cm, and node negative. Toxicity and cosmetic scoring were performed at 6 and 12 months. 98 patients (48%; 95% CI, 41-55%) experienced toxicity. Seven Grade 3 toxicities occurred (3.4%; 95% CI, 1.4-6.9%). Most patients (95%) had excellent or good cosmetic outcomes (95% CI, 91-98%) at 12 months. Most patients (94%) had little or no pigmentation change (95% CI, 90-97%), 88% little to no size change (95% CI, 82-92%), and 87% experienced minimal shape change (95% CI, 82-92%). Overall, Grade 3+ toxicity was rare and cosmetic outcomes were excellent. Severe toxicity with PB-IORT is similar to that reported in the TARGIT trial (3.3% rate of major toxicity) but lower than APBI (NSABP-39, 10.1% Grade 3/4 toxicities). We propose that the toxicity of PB-IORT compared with TARGIT and NSABP-39 is related to the radiation dose and delivery schedule. PB-IORT offers low-toxicity and good cosmetic outcomes when compared with other forms of APBI.


Enhanced intestinal excretion of hexachlorobenzene in rats by intraluminal injection of hexadecane.
The effect of hexadecane on the intestinal excretion of hexachlorobenzene was studied in female Sprague-Dawley rats dosed twice with 14C-hexachlorobenzene at 50 mg kg-1 per os. Injection of 75 mg n-hexadecane into ligated and unligated segments of the intestine increased concentrations of hexachlorobenzene in intestinal contents by about two- or three-fold in jejunal and ileal segments, and about two-fold in the cecal-colon segment. The jejunum appeared to be the site of greatest excretion of hexachlorobenzene followed by the ileum, the cecum and the colon. This order is opposite to our previous data from animals with an undisturbed intestinal passage. The apparently greater excretion of hexachlorobenzene into the small intestine is probably due to its much larger surface area than that of the large intestine. However, the residency time of luminal contents in the large intestine normally exceeds that in the small intestine by about 20--40-fold, which apparently more than compensates for the difference in relative surface area between small and large intestine. Thus, residency time appears to be a more important factor than surface area in determining the intestinal elimination of hexachlorobenzene. These results with hexachlorobenzene are probably typical of physiological disposition of lipophilic halogenated hydrocarbons generally.


Detection of immunoglobulin heavy chain IgG3 polymorphism in wild mice with xenogeneic monoclonal antibodies.
We have generated four xenogeneic rat antimouse IgG3 monoclonal antibodies recognizing at least three different antigenic determinants (epitopes) on BALB/c IgG3 molecules. These antibodies were used in solid-phase blocking radioimmunoassays for detection of the epitopes in sera of 40 inbred strains and 134 wild mice. These antibodies detect genetic polymorphism of IgG3 isotype among wild mice even though there is no polymorphism found among 40 inbred strains tested (except X-chromosome-linked immunodeficient CBA/N strain which lacks IgG3 molecules). An IgG3 variant was also isolated from hybridomas derived from Mus spretus.


Optimized production and characterization of a detergent-stable protease from Lysinibacillus fusiformis C250R.
In this study, we aimed to optimize the cultural and nutritional conditions for protease production by Lysinibacillus fusiformis strain C250R in submerged fermentation process using statistical methodology. The most significant factors (gruel, wheat bran, yeast extract, and FeSO4) were identified by Plackett-Burman design. Response surface methodology (RSM) was used to determine the optimum levels of the screened factors and their interaction. Under the optimized conditions, protease yield 3100U/mL was 4.5 folds higher than those obtained by the use of the initial conditions (680U/mL). Additionally, a new extracellular 51kDa-protease, designated SAPLF, was purified and biochemically characterized from strain C250R. It shows optimum activity at 70°C and pH 10. Its half-life times at 70 and 80°C were 10 and 6-h, respectively. Irreversible inhibition of enzyme activity of SAPLF with serine protease inhibitors demonstrated that it belongs to the serine protease family. Interestingly, its catalytic efficiency was higher than that of SPVP from Aeribacillus pallidus strain VP3 and Alcalase Ultra 2.5L from Bacillus licheniformis. This study demonstrated that SAPLF has a high detergent compatibility and an excellent stain removal compared to Alcalase Ultra 2.5L; which offers an interesting potential for its application in the laundry detergent industry.


Assessing the capacity for conflict and health research in Lebanon: a qualitative study.
Conflicts pose new challenges for health systems, requiring rapid and practical approaches to meet emerging needs on the ground. Lebanon has been highly influenced by surrounding conflicts in the Middle East and North Africa (MENA) region, especially the Syrian crisis. Strengthening research capacity to collect evidence on conflict in the MENA region and beyond is crucial to inform healthcare policy and practice. For targeted capacity strengthening interventions, the main objective of this paper is to present key findings of a needs assessment of conflict and health research in Lebanon. This will support recent efforts to scale up context-specific policies, interventions to strengthen the country's health system, and research capacity. The study is based on 30 semi-structured interviews with key informants such as specialist academics, humanitarian workers and public sector officials. Despite being ranked third in the number of publications on biomedical and health research per capita in MENA and in hosting reputable universities which are considered central academic hubs in the region, lack of nationwide research culture, insufficient funding and limited access to data were reported to be major challenges for health researchers in Lebanon. Even with the ongoing efforts, poor impact of research on policy continues to be a persistent gap. Large disparities in research capacities and taught skills were reported between different universities in Lebanon, with a disproportionate emphasis on quantitative over qualitative skills. Most medical students are not trained to conduct research or to practice in conflict settings. Concerns were also expressed regarding the ethics of research conducted, specifically by local non-governmental organizations. To conduct contextualized trainings on research skills with a stronger focus on qualitative approaches, medical practice, and ethical research in conflict. To better involve policymakers in designing research agendas by organizing multiple stakeholder meetings. The study indicates that health research in Lebanon is characterized by considerable strengths in terms of human capital and research capacities of certain universities. However, the Lebanese research infrastructure needs further development in terms of ensuring sustainable funding, providing access to data, teaching qualitative research skills, conducting ethical and multidisciplinary research, and promoting cross-sectoral knowledge transfer.


Over-expression of PR-10a leads to increased salt and osmotic tolerance in potato cell cultures.
The PR-10a protein (formerly STH-2) is known to be induced by biotic stress in potato. The present study demonstrates that transgenic suspension cells of the potato cultivar Desiree over-expressing the PR-10a protein exhibit significantly increased salt and osmotic tolerance compared to the respective wild type cells. A comparison of the proteome pattern of Solanum tuberosum suspension cultures cv. Desiree before and after the treatment with NaCl or sorbitol under equiosmolar conditions (740mOs/kg) revealed the pathogenesis related protein PR-10a to be one of the predominant differentially expressed proteins in potato cell cultures. The pr-10a mRNA was confirmed to be present by RT-PCR from salt challenged suspension cells and was transcribed into cDNA. For PR-10a over-expression Agrobacterium tumefaciens mediated transformation of the potato cells and a dicistronic vector harboring the cDNA of the pr-10a gene linked to a luciferase gene by an IRES (Internal Ribosome Binding Site) was used. The IRES mediated translation leads to co-expression of PR-10a and luciferase in a fixed ratio. By non-invasive luciferase assay homologous PR-10a over-expressing callus was identified after selection on phosphinothricin supplemented medium. This callus was used for the setup of a transgenic suspension culture. Along with increased salt and osmotic tolerance the transformed culture showed changed proline and glutathione levels under abiotic stress conditions in comparison to the wild type.


Case report: Right atrium-inferior vena cava bypass in a patient with unusual cardiac cystic echinococcosis.
Cardiovascular hydatid disease is caused by parasitic infection of Echinococcus granulosus, which could be asymptomatic or life-threatening depending on lesion site, granuloma size, and disease progression. Diagnosis and treatment of cardiac echinococcosis should be under comprehensive consideration. In this case, we reported a successful right atrium-inferior vena cava bypass surgery in a 31-year-old female with unresectable right atrial echinococcosis and inferior vena cava obstruction.


Malaria Trigram: improving the visualization of recurrence data for malaria elimination.
Although considerable success in reducing the incidence of malaria has been achieved in Brazil in recent years, an increase in the proportion of cases caused by the harder-to-eliminate Plasmodium vivax parasite can be noted. Recurrences in P. vivax malaria cases are due to new mosquito-bite infections, drug resistance or especially from relapses arising from hypnozoites. As such, new innovative surveillance strategies are needed. The aim of this study was to develop an infographic visualization tool to improve individual-level malaria surveillance focused on malaria elimination in the Brazilian Amazon. Action Research methodology was employed to deal with the complex malaria surveillance problem in the Amazon region. Iterative cycles were used, totalling four cycles with a formal validation of an operational version of the Malaria Trigram tool at the end of the process. Further probabilistic data linkage was carried out so that information on the same patients could be linked, allowing for follow-up analysis since the official system was not planned in such way that includes this purpose. An infographic user interface was developed for the Malaria Trigram that incorporates all the visual and descriptive power of the Trigram concept. It is a multidimensional and interactive historical representation of malaria cases per patient over time and provides visual input to decision-makers on recurrences of malaria. The Malaria Trigram is aimed to help public health professionals and policy makers to recognise and analyse different types of patterns in malaria events, including recurrences and reinfections, based on the current Brazilian health surveillance system, the SIVEP-Malária system, with no additional primary data collection or change in the current process. By using the Malaria Trigram, it is possible to plan and coordinate interventions for malaria elimination that are integrated with other parallel actions in the Brazilian Amazon region, such as vector control management, effective drug and vaccine deployment strategies.


Denaturation of supercoiled DNA: a Monte Carlo study.
A theoretical investigation of the denaturation characteristics of a supercoiled DNA has been presented employing a Metropolis Monte Carlo algorithm to examine the overall melting profiles of a supercoiled plasmid as the temperature is varied. We show that in contrast to a previously presented algorithm, this much simpler method is sufficient to explain almost all the overall denaturation characteristics and it also correctly calculates the detailed denaturation probabilities of each base pair at various degrees of supercoiling. We also present for the first time a theoretical investigation of the alkaline denaturation of a supercoiled plasmid. Although one can qualitatively reproduce the denaturation profiles using the present Monte Carlo algorithm, the agreement with experiment is not as good as in the case of thermal denaturation. The possible sources of discrepancy between theory and experiment have been discussed.