RayMVSNet++: Learning Ray-Based 1D Implicit Fields for Accurate Multi-View Stereo.
Learning-based multi-view stereo (MVS) has by far centered around 3D convolution on cost volumes. Due to the high computation and memory consumption of 3D CNN, the resolution of output depth is often considerably limited. Different from most existing works dedicated to adaptive refinement of cost volumes, we opt to directly optimize the depth value along each camera ray, mimicking the range (depth) finding of a laser scanner. This reduces the MVS problem to ray-based depth optimization which is much more light-weight than full cost volume optimization. In particular, we propose RayMVSNet which learns sequential prediction of a 1D implicit field along each camera ray with the zero-crossing point indicating scene depth. This sequential modeling, conducted based on transformer features, essentially learns the epipolar line search in traditional multi-view stereo. We devise a multi-task learning for better optimization convergence and depth accuracy. We found the monotonicity property of the SDFs along each ray greatly benefits the depth estimation. Our method ranks top on both the DTU and the Tanks & Temples datasets over all previous learning-based methods, achieving an overall reconstruction score of 0.33 mm on DTU and an F-score of 59.48% on Tanks & Temples. It is able to produce high-quality depth estimation and point cloud reconstruction in challenging scenarios such as objects/scenes with non-textured surface, severe occlusion, and highly varying depth range. Further, we propose RayMVSNet++ to enhance contextual feature aggregation for each ray through designing an attentional gating unit to select semantically relevant neighboring rays within the local frustum around that ray. This improves the performance on datasets with more challenging examples (e.g., low-quality images caused by poor lighting conditions or motion blur). RayMVSNet++ achieves state-of-the-art performance on the ScanNet dataset. In particular, it attains an AbsRel of 0.058m and produces accurate results on the two subsets of textureless regions and large depth variation.


Comparative Study of 27-Gauge versus 25-Gauge Vitrectomy for the Treatment of Primary Rhegmatogenous Retinal Detachment.
Purpose. To compare the vitrectomy time, clinical outcomes, and complications between 27-gauge (27-G) and 25-gauge (25-G) vitrectomy in patients with primary rhegmatogenous retinal detachment (PRRD). Methods. Prospective, nonrandomized, comparative, interventional study. Forty consecutive patients with PRRD were recruited. Twenty patients underwent the 27-gauge procedure and twenty patients had the 25-gauge procedure. The main outcome measure of the study was the actual vitrectomy time. Results. The mean duration of vitreous removal was 23.2 min (SD 6.5) with 27-G vitrectomy and 19.6 min (SD 7.3) with 25-G vitrectomy, resulting in a difference of 3.6 min (95% confidence interval (95%CI): -8.0 to 0.8 mins, p = 0.11). Mean logMAR visual acuity improved from 1.70 ± 1.18 preoperatively to 0.12 ± 0.14 at final postoperative visit (p < 0.001) in the 27-G group and from 1.52 ± 1.15 preoperatively to 0.22 ± 0.30 at final postoperative visit (p < 0.001) in the 25-G group. The anatomical success rate after a single operation was 90.0% and 85.0% in the 27-G and in the 25-G groups (p = 0.63), respectively. Intraoperative iatrogenic retinal breaks (IRBs) occurred in 2 eyes in the 27-G group and 1 eye in the 25-G group. Conclusions. Twenty-seven-gauge vitrectomy may be a safe and effective surgery for the treatment of PRRD.


Pancreatic Follicular Lymphoma Presenting as Acute Pancreatitis: Report of a Case.
Pancreatic B-cell lymphoma is rare; it accounts for 0.2% to 2.0% of extranodal non-Hodgkin lymphoma, and constitutes less than 0.5% of all pancreatic malignancies. Most histologic types of the pancreatic lymphoma are diffuse large B-cell lymphoma, and follicular lymphoma is quite rare. We report here a case of pancreatic follicular lymphoma that was initially detected by acute pancreatitis. This is the first reported case of pancreatic follicular lymphoma presenting with acute pancreatitis. A 71-year-old woman had epigastric and left upper quadrant abdominal pain. Computed tomography (CT) revealed features of acute pancreatitis. After standard therapy for pancreatitis, enhanced CT showed a pancreatic tumor (50 × 35 mm) in the body of the pancreas with gradual enhancement. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography showed a complete interruption of the pancreatic duct in the body, with mild dilation of the duct in the tail of the pancreas. Endoscopic ultrasonography revealed hypervascularity of the pancreatic tumor. The patient underwent distal pancreatectomy to remove the cause of pancreatitis and to disclose the diagnosis. Histologic examination revealed follicular lymphoma of pancreas. Despite recent improvement in clinical strategies, differential diagnosis between pancreatic lymphoma and pancreatic cancer is still difficult without histologic information. Pancreatic lymphoma should be considered as a differential diagnosis in a patient who initially presents with acute pancreatitis.


Repression of a herpes simplex virus immediate-early promoter by the Oct-2 transcription factor is dependent on an inhibitory region at the N terminus of the protein.
The B-cell form of the Oct-2 transcription factor Oct 2.1 can activate the herpes simplex virus immediate-early gene 3 (IE3) promoter, whereas the neuronally expressed Oct 2.4 and 2.5 forms of the protein, which contain a different C terminus, can repress this promoter. Here we show that partial or full deletion of the C terminus of Oct 2.1 in the presence of an intact N terminus results in a protein which can strongly repress the IE3 promoter. In contrast, deletion of the entire N terminus or a short region within it leaving the C terminus intact results in a very strong activator. Deletion of both N and C termini leaving only the isolated POU domain generates only a very weak repressor. The N-terminal region defined in this way can repress a heterologous promoter when linked to the DNA-binding domain of the GAL4 factor, indicating that it can function as an independent inhibitory domain. These results indicate that a specific region within the N terminus common to Oct 2.1, 2.4, and 2.5 plays a critical role in the ability of neuronally expressed forms of Oct-2 to repress the IE3 promoter but can do so only when the C-terminal region of Oct 2.1 is altered or deleted.


Streptococcus agalactiae infective endocarditis: analysis of 30 cases and review of the literature, 1962-1998.
We describe 30 cases (1.7%) of community-acquired penicillin-susceptible Streptococcus agalactiae endocarditis among 1771 episodes of endocarditis diagnosed in 4 Spanish hospitals from 1975 through 1998. Endocarditis affected a native valve (most often the mitral valve) in 25 cases (83%). Surgical valve replacement was performed for 12 patients (40%). Fourteen patients (47%) died. Mortality rates for patients with native and prosthetic valve endocarditis were 36% and 100%, respectively (P=.01). The mortality rate for native valve endocarditis decreased during the last 6 years of the study (from 61% in 1975-1992 to 8% in 1993-1998; P<.05). Additionally, 115 cases in the literature from 1962-1998 were reviewed. During 1980-1998, the percentage of patients who underwent cardiac surgery increased from 24% (in the previous period, 1962-1979) to 43% (P=.05) and the mortality rate decreased from 45% to 34% (P=NS). S. agalactiae is an uncommon cause of endocarditis with a high mortality rate, although the prognosis of native valve endocarditis has improved in recent years, probably because of an increased use of cardiac surgery.


Beyond static measures: A review of functional magnetic resonance spectroscopy and its potential to investigate dynamic glutamatergic abnormalities in schizophrenia.
Abnormalities of the glutamate system are increasingly implicated in schizophrenia but their exact nature remains unknown. Proton magnetic resonance spectroscopy (1H-MRS), while fundamental in revealing glutamatergic alterations in schizophrenia, has, until recently, been significantly limited and thought to only provide static measures. Functional magnetic resonance spectroscopy (fMRS), which uses sequential scans for dynamic measurement of a range of brain metabolites in activated brain areas, has lately been applied to a variety of task or stimulus conditions, producing interesting insights into neurometabolite responses to neural activation. Here, we summarise the existing 1H-MRS studies of brain glutamate in schizophrenia. We then present a comprehensive review of research studies that have utilised fMRS, and lastly consider how fMRS methods might further the understanding of glutamatergic abnormalities in schizophrenia.


Complete mitochondrial genome of the speckled dace Rhinichthys osculus, a widely distributed cyprinid minnow of western North America.
The speckled dace Rhinichthys osculus (order Cypriniformes), also known as the carpita pinta, is a small cyprinid minnow native to western North America. Here, we report the sequencing of the full mitochondrial genome (mitogenome) of R. osculus from a male fish collected from the Amargosa River Canyon in eastern California, USA. The assembled mitogenome is 16 658 base pair (bp) nucleotides, and encodes 13 protein-coding genes, and includes both a 12S and a 16S rRNA, 22 tRNAs, and a 985 bp D-loop control region. Mitogenome synteny reflects that of other Ostariophysian fishes with the majority of genes and RNAs encoded on the heavy strand (H-strand) except nd6, tRNA-Gln, tRNA-Ala, tRNA-Asn, tRNA-Cys, tRNA-Tyr, tRNA-Ser, tRNA-Glu, and tRNA-Pro. The availability of this R. osculus mitochondrial genome - the first complete mitogenome within the lineage of Rhinichthys riffle daces - provides a foundation for resolving evolutionary relationships among morphologically differentiated populations of R. osculus.


Is it culture or is it language? Examination of language effects in cross-cultural research on categorization.
Differences in reasoning styles between Chinese and European Americans held even when controlling for the language of testing. Bilingual Chinese organized objects in a more relational and less categorical way than European Americans, whether tested in English or in Chinese. Thus, culture affects categorization independent of the testing language. Nevertheless, language affected some Chinese bilinguals' categorization. The responses of Chinese from the Mainland and Taiwan were more relational when tested in Chinese than when tested in English. Responses of Chinese from Hong Kong and Singapore were equally relational when tested in Chinese and in English. Age and context of learning English are discussed to explain the differential language effects among different Chinese groups. Theoretical and methodological implications are discussed.


Allochimeric therapy induces unique regulatory T cells that mitigate chronic rejection.
Induction of tolerance to an allogeneic graft without the need for nonspecific immunosuppression is a major goal of transplantation therapy. We have shown that treatment with molecularly engineered, allochimeric [alpha(1h)(1/u)]-RT1.Aa class I MHC antigens bearing donor-type Wistar-Furth (WF, RT1.A(u)) or Lewis (LEW, RT1A(1)) amino acid substitutions for host-type ACI (RTI.A(a)) sequences in the alpha(1)-helical region induces donor-specific tolerance to cardiac allografts in rat recipients. The mechanisms involved in the establishment and maintenance of specific allograft tolerance are still not fully understood. It is now clear that acquisition of transplantation tolerance is an active, highly regulated, multistep process. According to the pool size model of allograft tolerance, the allograft outcome, rejection, or tolerance often depend on the balance between cytopathic and regulatory T cells (T-regs). This study examined mechanisms of chronic rejection (CR) development on a model of cardiac transplant tolerance after adoptive transfer of T-regs followed by allochimeric therapy. Generation of T-regs was demonstrated in vitro by MLR coculture and confirmed by adoptive transfer of T cells from primary recipients to secondary hosts. To confirm the true nature of regulatory cells, we performed a second transfer into tertiary recipients. Unlike T-regs from tolerant hosts, T cells from naive rats did not prolong graft survival. Histological evaluation of T-regs-transfected groups showed absence of visible CR. In contrast, T-regs generated in recipients after high-dose cyclosporine treatment failed to inhibit CR in transferred singeneic recipients. Allochimeric therapy triggers generation of unique regulatory lymphocytes that mitigate development of chronic rejection through regulation of anti-inflammatory mechanisms and down-regulation of alloantibody response.


Diagnosing lung cancer using etoposide microparticles labeled with 99mTc.
The diagnosis of lung cancer mostly occurs when the cancer is already in an advanced stage. In this situation, there are few options for the treatment and most of them have few chances of success. In this study, we developed and tested etoposide microparticles as a diagnostic agent for imaging lung cancer at early stages of development. We tested etoposide microparticles labeled with technetium 99m in inducted mice. The results demonstrated that over 10% of the total dose used was uptake by the tumor site. Also, the results showed that the microparticles had a good renal clearance and low uptake by liver and spleen. The data suggest that these micro-radiopharmaceuticals may be used for lung cancer imaging exam, especially single-photo emission computed tomography (SPECT).[Formula: see text].


Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring.
It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such as lifestyle, including diet, alcohol consumption, and smoking, as well as age and infections (viral or bacterial). Genetic and metabolic alterations such as obesity, gestational diabetes mellitus (GDM), and thyroidism alter epigenetic mechanisms, thereby contributing to neurodevelopmental disorders (NDs) such as embryonic neural tube defects (NTDs), autism, Down's syndrome, Rett syndrome, and later onset of neuropsychological deficits. This review comprehensively describes the recent findings in the epigenetic landscape contributing to altered molecular profiles resulting in NDs. Furthermore, we will discuss potential avenues for future research to identify diagnostic markers and therapeutic epi-drugs to reverse these abnormalities in the brain as epigenetic marks are plastic and reversible in nature.


Effects of parental monitoring, parent-child communication, and parents' expectation of the child's acculturation on the substance use behaviors of urban, Hispanic adolescents.
This cross-sectional study was conducted on 1,936 Hispanic adolescents of mean age 14.0 years (standard deviation= 0.4) from seven Los Angeles area schools. The effects of perceived parental monitoring and parent-child communication on the adolescents' self-reported past thirty day cigarette smoking and alcohol and marijuana use behaviors were analyzed. In addition, the relationships between parents' expectations of the child's acculturation and adolescents' drug use behaviors were examined. Parental monitoring and parent-child communication were found to have statistically significant inverse associations with all three drug types when controlling for one another and the demographic variables assessed in the study. Parents' expectation of the child's acculturation to the U.S. was found to be inversely related with alcohol use. Parental monitoring and parent-child communication were not found to mediate the relationship between parents' expectation of the child's acculturation and alcohol use.


Rhino-Orbito-Cerebral Mycosis and COVID-19: From Bad to Worse?
There has been an increase an alarming rise in invasive mycoses during COVID-19 pandemic, especially during the second wave. Compare the incidence of invasive mycoses in the last three years and study the risk factors, manifestations and outcomes of mycoses in the COVID era. Multicentric study was conducted across 21 centres in a state of western India over 12-months. The clinico-radiological, laboratory and microbiological features, treatment and outcomes of patients were studied. We also analysed yearly incidence of rhino-orbito-cerebral mycosis. There was more than five-times rise in the incidence of invasive mycoses compared to previous two-years. Of the 122 patients analysed, mucor, aspergillus and dual infection were seen in 86.9%, 4.1%, and 7.4% respectively. Fifty-nine percent had simultaneous mycosis and COVID-19 while rest had sequential infection. Common presenting features were headache (91%), facial pain (78.7%), diplopia (66.4%) and vison loss (56.6%). Rhino-orbito-sinusitis was present in 96.7%, meningitis in 6.6%, intracranial mass lesions in 15.6% and strokes in 14.8%. A total of 91.8% patients were diabetic, while 90.2% were treated with steroids during COVID-19 treatment. Mortality was 34.4%. Invasive fungal infections having high mortality and morbidity have increased burden on already overburdened healthcare system. Past illnesses, COVID-19 itself and its treatment and environmental factors seem responsible for the rise of fungal infection. Awareness and preventive strategies are the need of hours and larger studies are needed for better understanding of this deadly disease.


[Histopathological features and diagnostic considerations for genetic metabolic liver disease].
There are many kinds of genetic metabolic diseases, the causes are complicated, and both children and adults can develop diseases. Its diagnosis counts on finding clues from clinical data, and making diagnosis based on family history, symptoms and signs, laboratory examination, pathological examination and gene analysis. This article reviews the proper method of handling liver biopsy, histopathological pattern and characteristics as well as pathological and clinical diagnosis reports of genetic metabolic liver disease.


An irreducible juxta-epiphyseal fracture of the proximal phalanx. Report of a case.
The causes of irreducibility of juxta-epiphyseal fractures of the proximal phalanx are illustrated in a patient with button hole rent in the periosteum and extensor hood mechanism causing trapping of the distal fragment. The entrapment, in the manner of a Chinese finger trap, was aggravted by traction on the digit. Open reduction was necessary to reduce the fracture.


Testosterone undecanoate: a new orally active androgen.
Oral testosterone undecanoate (TU) in arachis oil has been evaluated with a view to its possible use as a means of androgen replacement therapy. A single 100 mg dose was found to elevate plasma androgen levels and urinary 17-ketosteroid excretion in 6 normal men. Ninety mg/day and 60 mg/day doses taken by a hypogonadal man resulted in sustained levels of androgen which appeared physiological when measured by radioimmunoassay without chromatography. However, upon separation of the steroids by chromatography it was found that much of the androgen present was in fact dihydrotestosterone not testosterone. Both TU and dihydrotestosterone undecanoate were detected in plasma by gas chromatography and it is suggested that the ester is absorbed as such from the intestine and the unesterified steroid subsequently released by hydrolysis. The convenience of oral administration, the resulting prolonged elevated plasma androgen levels and the probable lack of deleterious effects on the liver may render oral TU of value where androgen replacement therapy is indicated.


Effects of firm size on risks and reporting of elevation fall injury in construction trades.
Although many occupational safety programs are targeted toward large firms, the construction industry is dominated by smaller firms. This study examines the differential effect of firm size on the risk and the reporting of over 3000 serious and minor nonfatal elevation fall injuries in Danish construction industry trades (1993 to 1999). Small firms (<20 employees) accounted for 93% of all firms and 55% of worker-years. There was an inverse relationship between firm size and serious injury rates and a direct relationship between firm size and minor injury rates. An inverse relationship between firm size and injury severity odds ratios (serious versus minor) was found for carpentry, electrical work, general contracting, and the remaining other trades. Health and safety issues, legislation, and enforcement in the construction industry should, to a greater degree, be focused on smaller firms.


Biodegradation of Chemicals in Unspiked Surface Waters Downstream of Wastewater Treatment Plants.
The OECD 309 guideline uses spiked incubation tests to provide data on biodegradation kinetics in surface waters. However, potential limitations of spiking test chemicals into the studied water have not been investigated. We conducted the OECD 309 test with unspiked surface water relying on chemical residues present in the water. Parallel experiments were conducted with the same water spiked with 13 chemicals at higher concentrations (50 μg L-1). Six chemicals detected in both the spiked and the unspiked systems were biodegraded. For each chemical the concentration change over time differed between the systems. Tramadol and venlafaxine showed constant concentrations in the spiked systems but increasing concentrations in the unspiked systems. Atenolol and metoprolol showed first-order elimination with no lag in the unspiked systems, compared to a lag of 15-28 d followed by zero-order elimination kinetics in the spiked systems. Acesulfame was only slightly degraded (<50%) in the unspiked system, while removal was complete (>99%) in the spiked systems. Gabapentin displayed a complex behavior where the features differed markedly between the spiked and the unspiked systems. We conclude that spiking can strongly influence biodegradation, reducing the environmental relevance of test results. Under some conditions biodegradation can be measured in unspiked natural waters instead.


Prevalence of obesity and overweight in affluent adolescents from Ludhiana, Punjab.
The objective was to study the prevalence of obesity among adolescents in public schools of Ludhiana, catering to the affluent segment of population. We selected 1000 students from these schools by random, purposive sampling. Their anthropometry was taken. Students also filled-up a prevalidated questionnaire regarding dietary habits and lifestyle. Overweight/Obesity was defined using age and sex specific Body mass index (BMI) cut off points. Incidence of obesity was 3.4% and overweight was 12.7%. A significantly greater number of boys (15%) were overweight as compared to girls (10%).


A consistent integral equation theory for hard spheres.
The standard integral equation approach is used to extract the bridge function and other correlation functions of hard spheres fluid. To achieve this, we first use a recent consistent closure relation proposed by Bomont et al. [J. Chem. Phys. 119, 2188 (2003)] that has already proven to be accurate to describe the Lennard-Jones fluid properties. Second, we take advantage of the coherent scheme derived by Bomont [J. Chem. Phys. 119, 11484 (2003)] to calculate the excess chemical potential, the entropy and some relative transport properties. Very good agreement is obtained for structural quantities and thermodynamic properties as compared to exact data at densities ranging from 0.1 to 0.9.


[Cardiological problems in pheochromocytoma patients].
The course of the disease of six cases with pheochromocytoma was analyzed in patients, aged from 19 to 65, with manifestations mainly of the cardiovascular system. The diagnosis was verified in five of them at necropsy and in one of them--intraoperatively. The arterial hypertension accompanied by distinct vegetative symptomatics were the basic clinical signs and in some of the cases--disturbances in the carbohydrate metabolism. In four patients the arterial hypertension was permanent, in two of them--with paroxysmal elevation opresf blood pressure. In the other two--with hypertonic crises on the background normal blood pressure. The duration of the hypertension--from a single hypertonic crisis during pheochromocytoma attack, had a lethal end, till the fifth year. In three of the patients rhythm disorders (supraventricular tachycardia or tachyarrhythmia) originated in a pheochromocytoma paroxysm and in three--acute left ventricular insufficiency (gallop rhythm, pulmonary edema). The clinical picture resembles heart defect, myocardial infarction with congestive cardiac insufficiency and rhythm disorders, renal insufficiency with symptomatic arterial hypertension and decompensated hypertonic heart, epilepsy, coggagenosis . The authors admit that the development of acute left ventricular failure in hypertonic patients, that could hardly be explained only by the increase of the heart afterloading (in advanced age, not enlarged and no data about grve heart lesions) or the origination of severe rhythm disorders, not coped by the modern antirhythm agents, are signs, indicating, the existence of pheochromocytoma. The catecholamine affection of myocardium, that was found in three of the deceased patients, very likely, contributes to the origination of left ventricular failure.


The body fades away: investigating the effects of transparency of an embodied virtual body on pain threshold and body ownership.
The feeling of "ownership" over an external dummy/virtual body (or body part) has been proven to have both physiological and behavioural consequences. For instance, the vision of an "embodied" dummy or virtual body can modulate pain perception. However, the impact of partial or total invisibility of the body on physiology and behaviour has been hardly explored since it presents obvious difficulties in the real world. In this study we explored how body transparency affects both body ownership and pain threshold. By means of virtual reality, we presented healthy participants with a virtual co-located body with four different levels of transparency, while participants were tested for pain threshold by increasing ramps of heat stimulation. We found that the strength of the body ownership illusion decreases when the body gets more transparent. Nevertheless, in the conditions where the body was semi-transparent, higher levels of ownership over a see-through body resulted in an increased pain sensitivity. Virtual body ownership can be used for the development of pain management interventions. However, we demonstrate that providing invisibility of the body does not increase pain threshold. Therefore, body transparency is not a good strategy to decrease pain in clinical contexts, yet this remains to be tested.


A qualitative exploration of the client experience of inter-professional practice in the delivery of ActivePlus: a combined smoking cessation and physical activity intervention.
Research investigating interprofessional practice (IPP) frameworks has predominately focused on the service delivery of IPP or educating practitioners through interprofessional education. Minimal research has addressed client outcomes or the experience of clients with IPP in real world contexts. In this paper, we explore the experience of seven participants in the ActivePlus program, an IPP-based smoking cessation intervention combined with physical activity promotion. Participants informed on their program experiences through post-program in-depth interviews. A thematic analysis drew out themes pertaining to participant experiences of the joint practice element of the IPP model of care. Analysis identified two major themes: the joint practice experience, and the client-centered approach of the IPP model of care. Participants reflected on the ways that having two health practitioners in joint sessions benefited their intervention experience, as well as providing some critical feedback. Participants also reported observing and valuing aspects of client-centered practice that strengthened the rapport within the practitioner-client team and aided their behaviour change progress. The client-centered practice was instrumental in overcoming initial teething issues with joint session delivery and alleviating pre-program participant concerns about being outnumbered by multiple practitioners. Despite some early teething issues, participants reported a positive acceptance of the IPP and joint session delivery model, which added value to the overall ActivePlus program. Results from this research can provide practitioners with a client perspective on the key aspects they perceive as important in IPP joint session delivery. Further investigation into the client perception in similar interventions is recommended with larger samples and non-clinical groups.


Plasmin-induced migration requires signaling through protease-activated receptor 1 and integrin alpha(9)beta(1).
Plasmin is a major extracellular protease that elicits intracellular signals to mediate platelet aggregation, chemotaxis of peripheral blood monocytes, and release of arachidonate and leukotriene from several cell types in a G protein-dependent manner. Angiostatin, a fragment of plasmin(ogen), is a ligand and an antagonist for integrin alpha(9)beta(1). Here we report that plasmin specifically interacts with alpha(9)beta(1) and that plasmin induces of cells expressing migration recombinant alpha(9)beta(1) (alpha(9)-Chinese hamster ovary (CHO) cells). Migration was dependent on an interaction of the kringle domains of plasmin with alpha(9)beta(1) as well as the catalytic activity of plasmin. Angiostatin, representing the kringle domains of plasmin, alone did not induce the migration of alpha(9)-CHO cells, but simultaneous activation of the G protein-coupled protease-activated receptor (PAR)-1 with an agonist peptide induced the migration on angiostatin, whereas PAR-2 or PAR-4 agonist peptides were without effect. Furthermore, a small chemical inhibitor of PAR-1 (RWJ 58259) and a palmitoylated PAR-1-blocking peptide inhibited plasmin-induced migration of alpha(9)-CHO cells. These results suggest that plasmin induces migration by kringle-mediated binding to alpha(9)beta(1) and simultaneous proteolytic activation of PAR-1.


Pathophysiology of stroke: lessons from animal models.
The current pathophysiological understanding of stroke is substantially based on experimental studies. Brain injury after cerebral ischemia develops from a complex signaling cascade that evolves in an at least partially unraveled spatiotemporal pattern. Early excitotoxicity can lead to fast necrotic cell death, which produces the core of the infarction. The ischemic penumbra that surrounds the infarct core suffers milder insults. In this area, both mild excitotoxic and inflammatory mechanisms lead to delayed cell death, which shows biochemical characteristics of apoptosis. While brain cells are challenged by these deleterious mechanisms, they activate innate protective programs of the brain, which can be studied by means of experimentally inducing ischemic tolerance (i.e., ischemic preconditioning). Importantly, cerebral ischemia not only affects the brain parenchyma, but also impacts extracranial systems. For example, stroke induces a dramatic immunosuppression via an overactivation of the sympathetic nervous system. As a result, severe bacterial infections such as pneumonia occur. Complex signaling cascades not only decide about cell survival, but also about the neurological deficit and the mortality after stroke. These mechanisms of damage and endogenous protection present distinct molecular targets that are the rational basis for the development of neuroprotective drugs.


A retrospective study of six patients with mandibular metastatic carcinoma.
Mandibular metastatic carcinoma is a rare lesion that accounts for <1% of all oral malignancies. To provide greater experience in this field, the present study was conducted in which 6 cases of mandibular metastatic carcinoma were retrospectively reviewed. The origin of the lesions was the prostate in 2 cases, the lungs in 2 cases, the breast in 1 case and the thyroid gland in 1 case. The clinical and computed tomography features, surgical management and follow-up outcomes were investigated. The study indicated that surgeons should include the suspicion of metastasis in the differential diagnosis for mandibular tumor, particularly in patients who have a history of malignancy. A poor prognosis was associated with the examined patients. To extend the survival time as long as possible, a treatment strategy using multiple therapies, including segmental mandibulectomy, radiotherapy and chemotherapy, is recommended.


Subjective Social Status and Cardiovascular Reactivity: An Experimental Examination.
The present experiment examined the causal influence of subjective social status (SSS) on variables related to cardiovascular health [i.e., blood pressure, heart rate variability (HRV)]. Participants were randomly assigned to one of two conditions involving a social comparison that either induced a temporary shift toward high SSS or toward low SSS. Cardiovascular variables were measured before (baseline), throughout, and after the manipulation (recovery). Participants in the low SSS condition had a significantly lower HRV during experimental manipulation than at baseline (p = 0.001). They also showed a significantly stronger HRV reactivity compared to participants in the high SSS condition (p = 0.027). Our results suggest that already temporary shifts of one's SSS have measureable effects on cardiovascular variables. They support the notion that social status plays a causal role in the development of cardiovascular disease.


A new German Charité Jet Lag Scale for jet lag symptoms and application.
Travelling across multiple time zones provokes adaptation of endogenous circadian rhythm to the new time zone. Within the context of previous studies, an English-language state-of-health questionnaire, the Columbia Jet Lag Scale, is the only sufficiently validated scale for jet lag and its symptoms. This study presents a new state-of-health questionnaire in German, one intended to achieve standardisation of surveys on jet lag. The questionnaire was applied to define the baseline for the prevalence of jet lag symptoms based on a reference group (n = 36). The jet lag score ascertained was subsequently applied to determine the frequency of jet lag in a group of 53 subjects. Systematic investigation of the frequency of jet lag symptoms had not been previously presented. Among the group of 53 travelling test subjects, 60% demonstrated moderate jet lag symptoms. Practitioner Summary: This introduction of the Charité Jet Lag Scale, the first German jet lag questionnaire, calls attention to this topic for the first time since a 2000 publication in Ergonomics. Our systematic investigation of jet lag frequency, with the new scale, determined moderate jet lag symptoms among 60% of subjects.


Human mesenchymal stem cells (hMSCs) as targets of DNA damaging agents in cancer therapy.
Human mesenchymal stem cells (hMSCs) consist of cells that can differentiate into mesenchymal tissues, including osteoblasts, adipocytes and chondrocytes. hMSCs constitute a particular stem cell niche in the stromal compartment of the bone marrow, and also play a role in maintaining the normal function of haematopoietic stem cells. Furthermore, hMSCs localise to solid tumours, and can modulate cancer cell function through secretion of paracrine signals. While hMSCs, either in the bone marrow, or in the microenvironment of a tumour, will be targeted by DNA damaging agents used in cancer therapy, the response of the hMSC population to DNA damage is not well understood. In their role as progenitor cells, genomic DNA damage to hMSCs during cancer therapy could generate a population of surviving cells that can go on to give rise to secondary tumours. A better understanding of the response of hMSCs to DNA damage could provide new insights into the effects of cancer treatments, as well as into the development of treatment-associated secondary cancers. The article will review the relationship of hMSCs to cancer, with a focus on the response of hMSCs to DNA damaging agents.


Advanced endovascular techniques for thoracic and abdominal aortic dissections.
Endovascular treatment of aortic dissection is still in its infancy and consists usually of implantation of thoracic tubular stent-grafts to cover the proximal entry tear and redirect flow into the true lumen. Large registries comparing endovascular treatment by thoracic endovascular aortic repair (TEVAR) with open surgery for aortic dissection of the descending aorta have demonstrated a clear benefit for endovascular treatment with lower mortality and morbidity rates turning TEVAR into the standard treatment for complicated type B aortic dissection. With this momentum of success endovascular techniques continue to challenge open surgical techniques also in the aortic arch and the ascending aorta. TEVAR for aortic dissection has become more complex requiring an individualized treatment strategy as endovascular techniques have developed with the advent of new devices and increased experience of the operators. In many cases straight implantation of a thoracic tubular stent-graft is sufficient. But as rerouting of the blood flow can also change perfusion of vital side-branches the endovascular operator needs to have a large armamentarium of techniques and adjunctive procedures in order to sufficiently address the individual patient morphology. This chapter reviews a variety of endovascular techniques including access techniques, proximal sealing, the Petticoat-technique, false lumen deployment, fenestration techniques, branch vessel stenting and false lumen obstruction by various techniques.


Physiometabolic responses to road transport in weaned piglets for a short period and the effects of straw bedding.
The aim of the study was to evaluate the physiometabolic responses to stress in hybrid suckling piglets that were weaned and transported at different ages on a paved road under two vehicle conditions: with and without a layer of straw bedding. The piglets were weaned and transported at the following ages: 8, 15 and 22 days. The duration of each trip was 1 h. The piglets in each group were further divided into two sub-groups for two distinct experimental transport conditions: (1) over the road with straw bedding; and (2) over the same road but without straw bedding. A total of three repetitions were performed for each experimental condition. In order to assess their responses to weaning- and transport-induced stress, the study evaluated a thorough physiometabolic blood profile. The 8- and 15-day-old piglets transported without straw bedding showed increases in their pCO2, blood glucose, blood lactate levels and the percentage of hematocrit, but a decrease of pO2 upon arrival (P < 0.05). In contrast, the 22-day-old piglets transported on the same road with straw bedding were able to re-establish their blood concentrations of lactate, pCO2, pO2, Na+, K+, Ca2+ and pH during the trip (P < 0.05).


Single Rooted Permanent Premolars and Molars - A Rare Clinical Presentation Confirmed using Cone Beam Computed Tomography.
The morphology of the root and root canal system plays a significant role in the treatment outcome of endodontic procedures. The necessity of clear and high contrast images for tissues like bone and teeth has made the usage of newer imaging techniques inevitable. This is a rare case report wherein, the permanent posterior dentition of both arches was single rooted. While sporadic cases of single rooted teeth have been reported, it is rare for all the premolars and molars to show such variation. This rare clinical observation has been enhanced by Cone Beam Computed Tomography (CBCT), which provides a clear image with added benefits of 3D (Three Dimensional) image reconstruction, low dosage and rapid scan time.


Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytes.
3'-Hydroxyacetanilide orN-acetyl-meta-aminophenol (AMAP) is generally regarded as a non-hepatotoxic analog of acetaminophen (APAP). Previous studies demonstrated the absence of toxicity after AMAP in mice, hamsters, primary mouse hepatocytes and several cell lines. In contrast, experiments with liver slices suggested that it may be toxic to human hepatocytes; however, the mechanism of toxicity is unclear. To explore this,we treated primary human hepatocytes (PHH) with AMAP or APAP for up to 48 h and measured several parameters to assess metabolism and injury. Although less toxic than APAP, AMAP dose-dependently triggered cell death in PHH as indicated by alanine aminotransferase (ALT) release and propidium iodide (PI) staining. Similar to APAP, AMAP also significantly depleted glutathione (GSH) in PHH and caused mitochondrial damage as indicated by glutamate dehydrogenase (GDH) release and the JC-1 assay. However, unlike APAP, AMAP treatment did not cause relevant c-jun-N-terminal kinase (JNK) activation in the cytosol or phospho-JNK translocation to mitochondria. To compare, AMAP toxicity was assessed in primary mouse hepatocytes (PMH). No cytotoxicity was observed as indicated by the lack of lactate dehydrogenase release and no PI staining. Furthermore, there was no GSH depletion or mitochondrial dysfunction after AMAP treatment in PMH. Immunoblotting for arylated proteins suggested that AMAP treatment caused extensive mitochondrial protein adduct formation in PHH but not in PMH. In conclusion, AMAP is hepatotoxic in PHH and the mechanism involves the formation of mitochondrial protein adducts and mitochondrial dysfunction.


Identification of new ethanol-tolerant yeast strains with fermentation potential from central Patagonia.
The quest for new wild yeasts has increasingly gained attention because of their potential ability to provide unique organoleptic characters to fermented beverages. In this sense, Patagonia offers a wide diversity of ethanol-tolerant yeasts and stands out as a bioprospecting alternative. This study characterized the genetic and phenotypic diversity of yeast isolates obtained from Central Chilean Patagonia and analyzed their fermentation potential under different fermentative conditions. We recovered 125 colonies from Nothofagus spp. bark samples belonging to five yeast species: Saccharomyces eubayanus, Saccharomyces uvarum, Lachancea cidri, Kregervanrija delftensis, and Hanseniaspora valbyensis. High-throughput microcultivation assays demonstrated the extensive phenotypic diversity among Patagonian isolates, where Saccharomyces spp and L. cidri isolates exhibited the most outstanding fitness scores across the conditions tested. Fermentation performance assays under wine, mead, and beer conditions demonstrated the specific potential of the different species for each particular beverage. Saccharomyces spp. were the only isolates able to ferment beer wort. Interestingly, we found that L. cidri is a novel candidate species to ferment wine and mead, exceeding the fermentation capacity of a commercial strain. Unlike commercial strains, we found that L. cidri does not require nutritional supplements for efficient mead fermentation. In addition, L. cidri produces succinic and acetic acids, providing a distinct profile to the final fermented product. This work demonstrates the importance of bioprospecting efforts in Patagonia to isolate novel wild yeast strains with extraordinary biotechnological potential for the fermentation industry.


Risk Factors for Severe Enteroviral Infections in Children.
To study the risk factors associated with severe enterovirus infection among hospitalized pediatric patients with hand, foot, and mouth disease (HFMD) at King Narai Hospital, Lopburi, Thailand. We reviewed all of the suspected enterovirus infection cases aged less than 15 years admitted to King Narai Hospital between 2011 and 2013. Cases were classified into mild and severe enterovirus infection. Risk factors for severe enterovirus infection were analyzed using univariate and multivariate logistic regressions. During the study period, 156 patients met the case definition for further analysis. Of those 156 patients, 131 (84.0%) were classifed as mild cases, and 25 (16.0%) as severe cases with five (3.2%) deaths. The most common manifestations among the severe cases were seizures, pneumonia, meningoencephalitis, meningitis, and hyperglycemia. Of the 31 identifiable cases, 12 were caused by enterovirus 71 (EV71), 12 by coxsackievirus A16 (CA16), four by both, and three by other enterovirus. The clinical manifestations that were significantly related to severe enterovirus infection in univariate analysis were age of less than one year, highest body temperature greater than 39.0 degrees C, duration of fever greater than three days, absence of skin lesions, diarrhea, dyspnea, and hyperglycemia. The clinical manifestations that were significantly related to severe enterovirus infection by both univariate and multivariate analyses were absence of oral lesions, seizures, and drowsiness/lethargy. The major pathogens of severe disease were EV71 and CA16. High-risk factors significantly related to severe enterovirus infection in both univariate and multivariate analyses were absence of oral lesions, seizures, and drowsiness/lethargy. Early recognition of children at risk and prompt treatment is important to mitigate the deterioration of patients with enterovirus infection.


Hyperleptinemia in children with autosomal recessive spinal muscular atrophy type I-III.
Autosomal-recessive proximal spinal muscular atrophies (SMA) are disorders characterized by a ubiquitous deficiency of the survival of motor neuron protein that leads to a multisystemic disorder, which mostly affects alpha motor neurons. Disease progression is clinically associated with failure to thrive or weight loss, mainly caused by chewing and swallowing difficulties. Although pancreatic involvement has been described in animal models, systematic endocrinological evaluation of the energy metabolism in humans is lacking. In 43 patients with SMA type I-III (8 type I; 22 type II; 13 type III), aged 0.6-21.8 years, auxological parameters, pubertal stage, motor function (Motor Function Measurement 32 -MFM32) as well as levels of leptin, insulin glucose, hemoglobin A1c, Homeostasis Model Assessment index and an urinary steroid profile were determined. Hyperleptinemia was found in 15/35 (43%) of our patients; 9/15 (60%) of the hyperleptinemic patients were underweight, whereas 1/15 (7%) was obese. Hyperleptinemia was associated with SMA type (p = 0.018). There was a significant association with decreased motor function (MFM32 total score in hyperleptinemia 28.5%, in normoleptinemia 54.7% p = 0.008, OR 0.969; 95%-CI: 0.946-0.992). In addition, a higher occurrence of hirsutism, premature pubarche and a higher variability of the urinary steroid pattern were found. Hyperleptinemia is highly prevalent in underweight children with SMA and is associated with disease severity and decreased motor function. Neuronal degradation of hypothalamic cells or an increase in fat content by muscle remodeling could be the cause of hyperleptinemia.


Areas Requiring Restoration Efforts are a Complementary Opportunity to Support the Demand for Pollination Services in Brazil.
Crop pollination is one of Nature's Contributions to People (NCP) that reconciles biodiversity conservation and agricultural production. NCP benefits vary across space, including among distinct political-administrative levels within nations. Moreover, initiatives to restore ecosystems may enhance NCP provision, such as crop pollination delivered by native pollinators. We mapped crop pollination demand (PD), diversity of pollinator-dependent crops, and vegetation deficit (VD) (vis-a-vis Brazilian legal requirements) across all 5570 municipalities in Brazil. Pollinator-dependent crops represented ∼55% of the annual monetary value of agricultural production and ∼15% of the annual crop production. Municipalities with greater crop PD (i.e., higher degree of pollinator dependence of crop production) also had greater VD, associated with large properties and monocultures. In contrast, municipalities with a greater diversity of pollinator-dependent crops and predominantly small properties presented a smaller VD. Our results support that ecological restoration prompted by legal requirements offers great potential to promote crop productivity in larger properties. Moreover, conservation of vegetation remnants could support food security in small properties. We provided the first steps to identify spatial patterns linking biodiversity conservation and pollination service. Using Brazilian legal requirements as an example, we show that land-use management policies may be successfully used to ensure agricultural sustainability and crop production.


Paracervical Block for Laminaria Insertion Before Second-Trimester Abortion: A Randomized Controlled Trial.
To evaluate the efficacy of a paracervical block to decrease pain during osmotic dilator insertion before second-trimester abortion. In this double-blind, randomized trial, 41 women undergoing Laminaria insertion before a second-trimester abortion received either a paracervical block with 18 mL 1% lidocaine and 2 mL sodium bicarbonate or a sham block. Women were between 14 and 23 6/7 weeks of gestation. The primary outcome was pain immediately after insertion of Laminaria. Women assessed their pain on a 100-mm visual analog scale. Secondary outcomes included assessment of pain at other times during the insertion procedure and overall satisfaction with pain control. To detect a 25-mm difference in pain immediately after Laminaria insertion, at an α of 0.05 and 80% power, we aimed to enroll 20 patients in each arm. From May 2015 to December 2015, 20 women received a paracervical block and 21 received a sham block. Groups were similar in demographics, including parity, history of surgical abortion, and number of Laminaria placed. The paracervical block reduced pain after Laminaria insertion (median scores 13 mm [interquartile range 2-39] compared with 54 mm [interquartile range 27-61], P=.01, 95% CI -47.0 to -4.0). Women who received a paracervical block also reported higher satisfaction with overall pain control throughout the entire Laminaria insertion procedure (median scores 95 mm [interquartile range 78-100] compared with 70 mm [interquartile range 44-90], P=.05, 95% CI 0.0-37.0). Paracervical block is effective at reducing the pain of Laminaria insertion. Additionally, a paracervical block increases overall patient satisfaction with pain control during Laminaria placement. ClinicalTrials.gov, NCT02454296.


A gadolinium(III) complex of a carboxylic-phosphorus acid derivative of diethylenetriamine covalently bound to inulin, a potential macromolecular MRI contrast agent.
A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as contrast agent for magnetic resonance imaging (MRI) was synthesized. The structure of the chelate was derived from H5DTPA by replacing the central pendant arm by a phosphinic acid functional group, which was covalently bound to the polysaccharide inulin. On the average, each monosaccharide unit of the inulin was attached to approximately one (0.9) chelate moiety. The average molecular weight is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate oxygen atoms, and one P-O oxygen atom, and its first coordination sphere is completed by a water molecule. This compound shows promising properties for application as a contrast agent for MRI thanks to a favorable residence lifetime of this water molecule (170 ns at 298 K), a relatively long rotational correlation time (866 ps at 298 K), and the presence of two water molecules in the second coordination sphere of the Gd3+ ion. Furthermore, its stability toward transmetalation with Zn(II) is as high as that of the clinically used [Gd(DTPA)(H2O)]2-.


Digital Staining of High-Definition Fourier Transform Infrared (FT-IR) Images Using Deep Learning.
Histological stains, such as hematoxylin and eosin (H&E), are routinely used in clinical diagnosis and research. While these labels offer a high degree of specificity, throughput is limited by the need for multiple samples. Traditional histology stains, such as immunohistochemical labels, also rely only on protein expression and cannot quantify small molecules and metabolites that may aid in diagnosis. Finally, chemical stains and dyes permanently alter the tissue, making downstream analysis impossible. Fourier transform infrared (FT-IR) spectroscopic imaging has shown promise for label-free characterization of important tissue phenotypes and can bypass the need for many chemical labels. Fourier transform infrared classification commonly leverages supervised learning, requiring human annotation that is tedious and prone to errors. One alternative is digital staining, which leverages machine learning to map IR spectra to a corresponding chemical stain. This replaces human annotation with computer-aided alignment. Previous work relies on alignment of adjacent serial tissue sections. Since the tissue samples are not identical at the cellular level, this technique cannot be applied to high-definition FT-IR images. In this paper, we demonstrate that cellular-level mapping can be accomplished using identical samples for both FT-IR and chemical labels. In addition, higher-resolution results can be achieved using a deep convolutional neural network that integrates spatial and spectral features.


Leishmania major methionine sulfoxide reductase A is required for resistance to oxidative stress and efficient replication in macrophages.
Leishmania are protozoan parasites that proliferate within the phagolysome of mammalian macrophages. While a number of anti-oxidant systems in these parasites have been shown to protect against endogenous as well as host-generated reactive oxygen species, the potential role of enzymes involved in the repair of oxidatively damaged proteins remains uncharacterized. The Leishmania spp genomes encode a single putative methionine sulfoxide reductase (MsrA) that could have a role in reducing oxidized free and proteinogenic methionine residues. A GFP-fusion of L. major MsrA was shown to have a cytoplasmic localization by immunofluorescence microscopy and subcellular fractionation. An L. major msrA null mutant, generated by targeted replacement of both chromosomal allelles, was viable in rich medium but was unable to reduce exogenous methionine sulfoxide when cultivated in the presence of this amino acid, indicating that msrA encodes a functional MsrA. The ΔmsrA mutant exhibited increased sensitivity to H(2)O(2) compared to wild type parasites and was unable to proliferate normally in macrophages. Wild type sensitivity to H(2)O(2) and infectivity in macrophages was restored by complementation of the mutant with a plasmid encoding MsrA. Unexpectedly, the ΔmsrA mutant was able to induce normal lesions in susceptible BALB/c indicating that this protein is not essential for pathogenesis in vivo. Our results suggest that Leishmania MsrA contributes to the anti-oxidative defences of these parasites, but that complementary oxidative defence mechansims are up-regulated in lesion amastigotes.


SDA-CLIP: surgical visual domain adaptation using video and text labels.
Surgical action recognition is an essential technology in context-aware-based autonomous surgery, whereas the accuracy is limited by clinical dataset scale. Leveraging surgical videos from virtual reality (VR) simulations to research algorithms for the clinical domain application, also known as domain adaptation, can effectively reduce the cost of data acquisition and annotation, and protect patient privacy. We introduced a surgical domain adaptation method based on the contrastive language-image pretraining model (SDA-CLIP) to recognize cross-domain surgical action. Specifically, we utilized the Vision Transformer (ViT) and Transformer to extract video and text embeddings, respectively. Text embedding was developed as a bridge between VR and clinical domains. Inter- and intra-modality loss functions were employed to enhance the consistency of embeddings of the same class. Further, we evaluated our method on the MICCAI 2020 EndoVis Challenge SurgVisDom dataset. Our SDA-CLIP achieved a weighted F1-score of 65.9% (+18.9%) on the hard domain adaptation task (trained only with VR data) and 84.4% (+4.4%) on the soft domain adaptation task (trained with VR and clinical-like data), which outperformed the first place team of the challenge by a significant margin. The proposed SDA-CLIP model can effectively extract video scene information and textual semantic information, which greatly improves the performance of cross-domain surgical action recognition. The code is available at https://github.com/Lycus99/SDA-CLIP.


[Giant parathyroid carcinoma: diagnostic difficulties and therapeutic strategies].
Parathyroid carcinoma is a very rare malignancy responsible for 0.4 to 5.2% of hyperparathyroidism. Clinical diagnosis is difficult and treatment should be codified. Surgery is the only curative treatment. We report the case of a female patient treated for malignancy-associated hypercalcemia revealing parathyroid carcinoma. The patient underwent surgery; after three months she developed lymphatic recurrence. Given the absence of other secondary involvement, bilateral lymph node dissection followed by chemotherapy was performed. Parathyroid carcinoma is often suspected on the basis of biological, radiological and especially intraoperative macroscopic criteria, but definitive diagnosis is made histopathologically. Surgery is currently the only curative treatment and the role of adjuvant therapy is to establish.


Multi-omics characterization of the microbial populations and chemical space composition of a water kefir fermentation.
In recent years, the popularity of fermented foods has strongly increased based on their proven health benefits and the adoption of new trends among consumers. One of these health-promoting products is water kefir, which is a fermented sugary beverage based on kefir grains (symbiotic colonies of yeast, lactic acid and acetic acid bacteria). According to previous knowledge and the uniqueness of each water kefir fermentation, the following project aimed to explore the microbial and chemical composition of a water kefir fermentation and its microbial consortium, through the integration of culture-dependent methods, compositional metagenomics, and untargeted metabolomics. These methods were applied in two types of samples: fermentation grains (inoculum) and fermentation samples collected at different time points. A strains culture collection of ∼90 strains was established by means of culture-dependent methods, mainly consisting of individuals of Pichia membranifaciens, Acetobacter orientalis, Lentilactobacillus hilgardii, Lacticaseibacillus paracasei, Acetobacter pomorum, Lentilactobacillus buchneri, Pichia kudriavzevii, Acetobacter pasteurianus, Schleiferilactobacillus harbinensis, and Kazachstania exigua, which can be further studied for their use in synthetic consortia formulation. In addition, metabarcoding of each fermentation time was done by 16S and ITS sequencing for bacteria and yeast, respectively. The results show strong population shifts of the microbial community during the fermentation time course, with an enrichment of microbial groups after 72 h of fermentation. Metataxonomics results revealed Lactobacillus and Acetobacter as the dominant genera for lactic acid and acetic acid bacteria, whereas, for yeast, P. membranifaciens was the dominant species. In addition, correlation and systematic analyses of microbial growth patterns and metabolite richness allowed the recognition of metabolic enrichment points between 72 and 96 h and correlation between microbial groups and metabolite abundance (e.g., Bile acid conjugates and Acetobacter tropicalis). Metabolomic analysis also evidenced the production of bioactive compounds in this fermented matrix, which have been associated with biological activities, including antimicrobial and antioxidant. Interestingly, the chemical family of Isoschaftosides (C-glycosyl flavonoids) was also found, representing an important finding since this compound, with hepatoprotective and anti-inflammatory activity, had not been previously reported in this matrix. We conclude that the integration of microbial biodiversity, cultured species, and chemical data enables the identification of relevant microbial population patterns and the detection of specific points of enrichment during the fermentation process of a food matrix, which enables the future design of synthetic microbial consortia, which can be used as targeted probiotics for digestive and metabolic health.


FFMAVP: a new classifier based on feature fusion and multitask learning for identifying antiviral peptides and their subclasses.
Antiviral peptides (AVPs) are widely found in animals and plants, with high specificity and strong sensitivity to drug-resistant viruses. However, due to the great heterogeneity of different viruses, most of the AVPs have specific antiviral activities. Therefore, it is necessary to identify the specific activities of AVPs on virus types. Most existing studies only identify AVPs, with only a few studies identifying subclasses by training multiple binary classifiers. We develop a two-stage prediction tool named FFMAVP that can simultaneously predict AVPs and their subclasses. In the first stage, we identify whether a peptide is AVP or not. In the second stage, we predict the six virus families and eight species specifically targeted by AVPs based on two multiclass tasks. Specifically, the feature extraction module in the two-stage task of FFMAVP adopts the same neural network structure, in which one branch extracts features based on amino acid feature descriptors and the other branch extracts sequence features. Then, the two types of features are fused for the following task. Considering the correlation between the two tasks of the second stage, a multitask learning model is constructed to improve the effectiveness of the two multiclass tasks. In addition, to improve the effectiveness of the second stage, the network parameters trained through the first-stage data are used to initialize the network parameters in the second stage. As a demonstration, the cross-validation results, independent test results and visualization results show that FFMAVP achieves great advantages in both stages.


[Hospitals between present and future].
What role will hospitals play in the future of the healthcare system, and how this role will be changing? Hospitals of the future will confront difficult challanges: new kinds of disease, rapidly evolving medical technologies, aging of the population and evolving budget restrictions. All features that make it difficult to foresee the hospital of the future. The aim of this paper is to analyze the different challanges that hospital have to face in a modern scenario of evolution of public health services.


[Expanding outpatient rehabilitation].
Up to now, the majority of rehabilitative measures in Germany has been performed in inpatient programmes. In the past 10 years an extension of outpatient rehabilitation can be noted. Because of new social welfare legislation the legal disadvantages for participants in outpatient rehabilitation have been eliminated on the 1st July 2001. In the past year, the Federal Rehabilitation Council as well as various rehabilitation providers have developed further and specified their concepts in outpatient rehabilitation. Concept requirements include still the principles of holism, interdisciplinarity, goal-oriented rehabilitation and team-work of rehabilitation staff. The extension of outpatient rehabilitation in the sphere of German pension insurance scheme is documented by the increase in models respectively regular services and rehabilitative measures. The results of the evaluation suggest, that the outpatient realisation of a comprehensive rehabilitation concept yields comparable results as the inpatient realisation. In some regions there is a strong cooperation between pension insurance institutes and corresponding health insurance companies in order to extend outpatient rehabilitation. A quality assurance program for outpatient rehabilitation will be developed. It can be expected, that the extension of outpatient rehabilitation goes on and that thereby the possibilities of a more flexible medical rehabilitation grow.


Cardiac autonomic neuropathy predicts diabetic retinopathy progression in Asian population with type 2 diabetes mellitus.
To investigate the role of cardiac autonomic neuropathy (CAN), vascular condition, and sensory function in diabetic retinopathy (DR) progression. This 3-year cohort study conducted in a community hospital included 4850 patients over 20 with type 2 diabetes mellitus. Participants were assessed in 2017 at baseline and were followed up in 2020. Patients were divided into two groups based on whether they had DR progression or not and were compared using the chi-square test or two-sample t-test. Beta coefficient and odds ratio (OR) with 95% confidence intervals were calculated using binary logistic regression. The receiver operating characteristic (ROC) curve of various independent variables for DR progression was provided with C-statistics. Abnormal hemoglobin A1c (HbA1c) level/variation, estimated glomerular filtration rate, urine albumin-to-creatinine ratio, R-R interval variation, standard deviation of the average NN intervals, autonomic nervous system function, power of high-frequency (HF) bands, balance, cardio-ankle vascular index (CAVI), and warm stimulation (WS) were associated with DR progression. Average HbA1c, HF, and proliferative diabetic retinopathy were independent factors for patients developing DR progression. The top three areas under the curve of ROCs were HF + baseline DR grading, WS + baseline DR grading, and CAVI + baseline DR grading. These variable combinations were the most reliable predictors of DR progression. CAN, abnormal vascular condition, and sensory function are associated with DR progression. The combination of HF, WS, and CAVI with baseline DR grading provides the most accurate predictive model for DR progression. Early detection of these factors is important to prevent DR progression.


The molecular grammar of protein disorder guiding genome-binding locations.
Intrinsically disordered regions (IDRs) direct transcription factors (TFs) towards selected genomic occurrences of their binding motif, as exemplified by budding yeast's Msn2. However, the sequence basis of IDR-directed TF binding selectivity remains unknown. To reveal this sequence grammar, we analyze the genomic localizations of >100 designed IDR mutants, each carrying up to 122 mutations within this 567-AA region. Our data points at multivalent interactions, carried by hydrophobic-mostly aliphatic-residues dispersed within a disordered environment and independent of linear sequence motifs, as the key determinants of Msn2 genomic localization. The implications of our results for the mechanistic basis of IDR-based TF binding preferences are discussed.


Morphological alterations and NO-synthase expression in the heart after continuous light exposure of rats.
Although exposure to continuous light is associated with hypertension and modulates the outcome of ischemia-reperfusion injury, less attention has been paid to its effects on cardiac morphology. We investigated whether 4-week exposure of experimental rats to continuous 24 h/day light can modify cardiac morphology, with focus on heart weight, fibrosis and collagen I/III ratio in correlation with NO-synthase expression. Two groups of male adult Wistar rats were studied: controls exposed to normal light/dark cycle (12 h/day light, 12 h/day dark) and rats exposed to continuous light. After 4 weeks of treatment the absolute and the relative heart weights were determined and myocardial fibrosis and collagen type I/III ratio were evaluated using picrosirius red staining. Endothelial and inducible NO-synthase expression was detected immunohistochemically. The exposure of rats to continuous light resulted in an increase of body weight with proportionally increased heart weight. Myocardial fibrosis remained unaffected but collagen I/III ratio increased. Neither endothelial nor inducible NO-synthase expression was altered in light-exposed rats. We conclude that the loss of structural homogeneity of the myocardium in favor of collagen type I might increase myocardial stiffness and contribute to functional alterations after continuous light exposure.


Obesity and liver transplantation.
The percentage of overweight and obese patients (OPs) waiting for a liver transplant continues to increase. Despite the significant advances occurred in bariatric medicine, obesity is still considered a relative contraindication to liver transplantation (LT). The main aim of this review is to appraise the literature on the outcomes of OPs undergoing LT, treatments that might reduce their weight before, during or after surgery, and discuss some of the controversies and limitations of the current knowledge with the intent of highlighting areas where future research is needed.


Eels of the genus Bathyuroconger in the northwestern Pacific, with descriptions of four new species (Anguilliformes: Congridae).
Examination of the congrid genus Bathyuroconger in the northwestern Pacific reveals six species are present. Bathyuroconger albus sp. nov. differs from congeners in having a pale coloration, a moderately reduced gill opening that is close to but not touching the pectoral-fin base, trunk length 2.0-2.9 times HL, preanal vertebrae 45-54, preanal lateral-line pores 42-48. Bathyuroconger dolichosomus sp. nov. has a moderately reduced gill opening that is close to but not touching the pectoral-fin base, trunk length 3.2 times HL, preanal vertebrae 63, and preanal lateral-line pores 61. Bathyuroconger fowleri sp. nov. has a small gill opening distant from the pectoral-fin base, trunk length 1.7-2.1 times head length, dorsal-fin origin over middle of pectoral fin, predorsal vertebrae 10-14, preanal vertebrae 48-52, total vertebrae 173-178. Bathyuroconger hawaiiensis sp. nov. has a slightly reduced gill opening, separated from the pectoral-fin base, dark color, total vertebrae 201-210. Bathyuroconger parvibranchialis (Fowler, 1934), redescribed herein, has a small gill opening distant from the pectoral-fin base, dorsal-fin origin over base of pectoral fin, trunk length 1.4-1.7 times in HL, preanal vertebrae 43-48, total vertebrae 181-189, and a uniformly dark color in adults. Bathyuroconger cf. vicinus has a full-size gill opening in contact with pectoral-fin base, dark color, and total vertebrae 196-201. A key to the species in the northwestern Pacific is provided.


[Theanine affects sedative effect of pentobarbital sodium in ICR mice].
To evaluate the effects of theanine on sedative effects induced by pentobarbital sodium. The locomotor activities of ICR mice induced by theanine (0.25, 0.5, 1.0, 2.0, 4.0 g x kg(-1)), pentobarbital sodium (5, 10 mg x kg(-1)) or the combination of both were determined with video-tracking system, and a novel index: Peripheral active time Peripheral time (PATP) was established. Hypnosis effect of combination of both was tested with right-reflex disappearance. Compared with normal saline (74.52 +/- 20.4)%, theanine alone decreased this PATP in dose-dependent manner from (62.03 +/- 21.11)%, (56.44 +/- 21.69)%, (31.13 +/- 17.2)%, (25.06 +/- 10.03)% to (17.21 +/- 7.43)% (P>0.05, P<0.05, P<0.01, P<0.01 and P<0.01, respectively). Compared with pentobarbital sodium (5 mg x kg(-1)), between 0.25 g x kg(-1) and 1.0 g x kg(-1) theanine combined with that decreased peripheral PATP from (28.30 +/- 17.57)%, (30.64 +/- 17.21)% to (24.28 +/- 9.59)% (all P<0.01), and increased by 2.0 g x kg(-1) reversely (61.95 +/- 19.39)%. Compared with normal saline, pentobarbital sodium (10 mg x kg(-1)) and the combination with theanine decreased significantly PATP (all P<0.01). Compared with pentobarbital sodium (10 mg x kg(-1)), 0.25 g x kg(-1) theanine combined with that increased PATP [(25.37 +/- 13.68)% vs (10.08 +/- 7.98)%, P<0.01)] and 0.5 g x kg(-1), 1.0 g x kg(-1) theanine could depresse that increase [(14.56 +/-10.10)%, (8.24 +/- 4.08)% vs (10.08 +/- 7.98)%]. Total distance and peripheral active time showed the same or similar tendency in theanine alone or combination with pentobarbital sodium . Theanine enchanced hypnosis effect of pentobarbital sodium in dose-dependent manner. Theanine can affect the sedative effect of low dose pentobarbital sodium in bidirectional action style but not change the hypnosis effect.


Role of oral antibiotics for prophylaxis against surgical site infections after elective colorectal surgery.
Over the past few decades, surgeons have made many attempts to reduce the incidence of surgical site infections (SSI) after elective colorectal surgery. Routine faecal diversion is no longer practiced in elective colonic surgery and mechanical bowel preparation is on the verge of being eliminated altogether. Intravenous antibiotics have become the standard of care as prophylaxis against SSI for elective colorectal operations. However, the role of oral antibiotics is still being debated. We review the available data evaluating the role of oral antibiotics as prophylaxis for SSI in colorectal surgery.


Breeding research on sake yeasts in Japan: history, recent technological advances, and future perspectives.
Sake is an alcoholic beverage of Japan, with a tradition lasting more than 1,300 years; it is produced from rice and water by fermenting with the koji mold Aspergillus oryzae and sake yeast Saccharomyces cerevisiae. Breeding research on sake yeasts was originally developed in Japan by incorporating microbiological and genetic research methodologies adopted in other scientific areas. Since the advent of a genetic paradigm, isolation of yeast mutants has been a dominant approach for the breeding of favorable sake yeasts. These sake yeasts include (a) those that do not form foams (produced by isolating a mutant that does not stick to foams, thus decreasing the cost of sake production); (b) those that do not produce urea, which leads to the formation of ethyl carbamate, a possible carcinogen (isolated by positive selection in a canavanine-, arginine-, and ornithine-containing medium); (c) those that produce an increased amount of ethyl caproate, an apple-like flavor (produced by isolating a mutant resistant to cerulenin, an inhibitor of fatty-acid synthesis); and (d) those that produce a decreased amount of pyruvate (produced by isolating a mutant resistant to an inhibitor of mitochondrial transport, thus decreasing the amount of diacetyl). Given that sake yeasts perform sexual reproduction, sporulation and mating are potent approaches for their breeding. Recently, the genome sequences of sake yeasts have been determined and made publicly accessible. By utilizing this information, the quantitative trait loci (QTLs) for the brewing characteristics of sake yeasts have been identified, which paves a way to DNA marker-assisted selection of the mated strains. Genetic engineering technologies for experimental yeast strains have recently been established by academic groups, and these technologies have also been applied to the breeding of sake yeasts. Sake yeasts whose genomes have been modified with these technologies correspond to genetically modified organisms (GMOs). However, technologies that enable the elimination of extraneous DNA sequences from the genome of sake yeast have been developed. Sake yeasts genetically modified with these technologies are called self-cloning yeasts and do not contain extraneous DNA sequences. These yeasts were exempted from the Japanese government's guidelines for genetically modified food. Protoplast fusion has also been utilized to breed favorable sake yeasts. Future directions for the breeding of sake yeasts are also proposed in this review. The reviewed research provides perspectives for the breeding of brewery yeasts in other fermentation industries.


The unique function of the Arabidopsis circadian clock gene PRR5 in the regulation of shade avoidance response.
Shade avoidance response (S.A.R) is regulated by light and circadian clock. Circadian clock controls S.A.R by the transcriptional regulation of positive regulators of S.A.R, PIF4 and PIF5, to prevent plants from responding to 'light' of dark period. Thus, in many cases, deficits in circadian clock appear in abnormalities of hypocotyl and/or petiole elongation. Previously, interesting phenomena were reported that the triple mutants of PSEUDO RESPONSE REGULATORS9, 7 and 5, which are clock components, show longer petioles and smaller leaves under light/dark cycle than those under continuous lighting. These S.A.R-like phenotypes cannot be explained by their hyposensitivity to red light. We demonstrated detailed analyses of this mutant to reveal the leaf-specific S.A.R regulated by circadian clock. Expression analyses of S.A.R-related genes suggested that PRR5 functions as a repressor of S.A.R. Morphological analyses of leaves under different light condition revealed that PRR5 is involved in the inhibition of leaf expansion in S.A.R.


NOTCH Signaling in Aortic Valve Development and Calcific Aortic Valve Disease.
NOTCH intercellular signaling mediates the communications between adjacent cells involved in multiple biological processes essential for tissue morphogenesis and homeostasis. The NOTCH1 mutations are the first identified human genetic variants that cause congenital bicuspid aortic valve (BAV) and calcific aortic valve disease (CAVD). Genetic variants affecting other genes in the NOTCH signaling pathway may also contribute to the development of BAV and the pathogenesis of CAVD. While CAVD occurs commonly in the elderly population with tri-leaflet aortic valve, patients with BAV have a high risk of developing CAVD at a young age. This observation indicates an important role of NOTCH signaling in the postnatal homeostasis of the aortic valve, in addition to its prenatal functions during aortic valve development. Over the last decade, animal studies, especially with the mouse models, have revealed detailed information in the developmental etiology of congenital aortic valve defects. In this review, we will discuss the molecular and cellular aspects of aortic valve development and examine the embryonic pathogenesis of BAV. We will focus our discussions on the NOTCH signaling during the endocardial-to-mesenchymal transformation (EMT) and the post-EMT remodeling of the aortic valve. We will further examine the involvement of the NOTCH mutations in the postnatal development of CAVD. We will emphasize the deleterious impact of the embryonic valve defects on the homeostatic mechanisms of the adult aortic valve for the purpose of identifying the potential therapeutic targets for disease intervention.


"The visible skeleton series": the art of Laura Ferguson.
Laura Ferguson's The Visible Skeleton Series constitutes an artistic self-representation of scoliosis. Ferguson employs high-tech medical imaging and innovative graphical techniques to suggest a novel view of her skeletal "deformity." This section presents introductions to the series by a historian of medicine and by the artist herself, and offers personal and professional reflections on the work from an orthopedic surgeon, a social worker with lived experience of cleft lip, and a retired pediatric forensic pathologist.


Differential processing of let-7a precursors influences RRM2 expression and chemosensitivity in pancreatic cancer: role of LIN-28 and SET oncoprotein.
Overexpression of ribonucleotide reductase subunit M2 (RRM2), involved in deoxyribonucleotide synthesis, drives the chemoresistance of pancreatic cancer to nucleoside analogs (e.g., gemcitabine). While silencing RRM2 by synthetic means has shown promise in reducing chemoresistance, targeting endogenous molecules, especially microRNAs (miRNAs), to advance chemotherapeutic outcomes has been poorly explored. Based on computational predictions, we hypothesized that the let-7 tumor suppressor miRNAs will inhibit RRM2-mediated gemcitabine chemoresistance in pancreatic cancer. Reduced expression of the majority of let-7 miRNAs with an inverse relationship to RRM2 expression was identified in innately gemcitabine-resistant pancreatic cancer cell lines. Direct binding of let-7 miRNAs to the 3' UTR of RRM2 transcripts identified post-transcriptional regulation of RRM2 influencing gemcitabine chemosensitivity. Intriguingly, overexpression of human precursor-let-7 miRNAs led to differential RRM2 expression and chemosensitivity responses in a poorly differentiated pancreatic cancer cell line, MIA PaCa-2. Defective processing of let-7a precursors to mature forms, in part, explained the discrepancies observed with let-7a expressional outcomes. Consistently, the ratios of mature to precursor let-7a were progressively reduced in gemcitabine-sensitive L3.6pl and Capan-1 cell lines induced to acquire gemcitabine resistance. Besides known regulators of let-7 biogenesis (e.g., LIN-28), short hairpin RNA library screening identified several novel RNA binding proteins, including the SET oncoprotein, to differentially impact let-7 biogenesis and chemosensitivity in gemcitabine-sensitive versus -resistant pancreatic cancer cells. Further, LIN-28 and SET knockdown in the cells led to profound reductions in cellular proliferation and colony-formation capacities. Finally, defective processing of let-7a precursors with a positive correlation to RRM2 overexpression was identified in patient-derived pancreatic ductal adenocarcinoma (PDAC) tissues. These data demonstrate an intricate post-transcriptional regulation of RRM2 and chemosensitivity by let-7a and that the manipulation of regulatory proteins involved in let-7a transcription/processing may provide a mechanism for improving chemotherapeutic and/or tumor growth control responses in pancreatic cancer.


Effect of androgen ablation on prostatic cell differentiation in dogs.
This study was conducted to gain further insight into the role of androgen in maintaining a balanced prostate gland growth in dogs. Effects of castration on prostatic cell were assessed by comparing the expression level of high molecular weight cytokeratin (HMW), alpha-actin, and vimentin in intact and castrated dogs. Mature dogs were castrated while they were under general anesthesia and were killed after 1 month. Mature prostate gland structures from intact dogs are characterized by the presence of differentiated columnar secretary epithelial cells and progenitor basal cells that are located within acini and ducts embedded in a thin fibromuscular tissue. Basal cells were distinguished from secretory epithelial cells by HMW cytokeratin immunostaining, which is expressed specifically by basal cells but not by epithelial cells. Castration-induced secretory epithelial cell death, leave the basal cells intact to form a continuous layer lining the atrophied acini. However, the survived basal cells lost their capacity to differentiate to secretory epithelial cells. In addition, androgen ablation induced remarkable reorganization of the cellular components of the fibromuscular compartment. In intact dogs, this compartment of prostate gland is composed mainly of differentiated smooth muscles and scattered mesenchymal muscles as reflected by the high and low actin and vimentin expressions, respectively. Castration for 1 month induced a progressive shift toward mesenchymal cells, which appeared to occupy most of the fibromuscular compartment. Based on these findings, it appears that androgen acts to maintain a steady state of prostate gland by driving the differentiation of prostatic cells and by maintaining its fully differentiated state.


Tanshinone IIA promotes cardiac differentiation and improves cell motility by modulating the Wnt/β‑catenin signaling pathway.
Although the cardiovascular pharmacological actions of Tanshinone IIA (TanIIA) have been extensively studied, research on its roles in cardiac regeneration is still insufficient. The present study employed the cardiac myoblast cell line H9c2 to evaluate the possible roles of TanIIA in cardiac regeneration. It was found that certain concentration of TanIIA inhibited cell proliferation by suppressing the expression of proteins related to the cell cycle [cyclin dependent kinase (CDK)4, CDK6 and cyclin D1] and proliferation [c‑Myc, octamer‑binding transcription factor 4 (Oct4) and proliferating cell nuclear antigen (PCNA)] without inducing apoptosis. In this process, the expression of cardiac troponin in the treated cells was significantly increased and the migration of the treated cells toward the wound area was significantly enhanced. Meanwhile, TanIIA inhibited the canonical signaling pathway through increasing the expression of glycogen synthase kinase 3β (GSK‑3β) and adenomatous polyposis coli (APC) and increased the expression of Wnt11 and Wnt5a in the noncanonical Wnt signaling pathway. Following β‑catenin agonist WAY‑262611 intervention, the effect of TanIIA on the promotion of cardiac differentiation and improved cell migration was significantly reduced. In conclusion, it was hypothesized that TanIIA could promote cardiac differentiation and improve cell motility by modulating the Wnt/β‑catenin signaling pathway. These results suggest that TanIIA may play beneficial roles in myocardial regeneration following stem cell transplantation.


Effects of TGF-beta 1 on interleukin profile of human dental pulp and odontoblasts.
Transforming growth factor-beta 1 (TGF-beta1) is the most extensively studied growth factor in dentin-pulp complex, with pleiotropic effects on pulp response and healing. Our main objective was to analyze the expression profile of pulp tissue and odontoblasts, and the effects of TGF-beta1 on these profiles in cultured human pulp and odontoblasts with a specific interest in the anti- and pro-inflammatory cytokines. For that purpose, pulps and odontoblasts were cultured for different time periods, and microarray was performed to both cultured and native samples. Of cytokines, various interleukins (IL) were confirmed by RT-PCR, and in +/- TGF-beta1 treated pulps also by antibody array. Pro-inflammatory IL-7, -12alpha and -16 mRNAs were detected in native pulp. The expression levels of pro-inflammatory IL-1alpha, -1beta, -6 and -8 were clearly induced after TGF-beta1 treatment, while no anti-inflammatory cytokines were induced. Of all pulpal interleukins analyzed IL-6 and -8 were present at the highest levels in conditioned pulp tissue media. In native odontoblasts pro-inflammatory IL-6 and -7 mRNAs were detected, and in cultured odontoblasts pro-inflammatory IL-8 mRNA showed over 20-fold transient induction after TGF-beta1 treatment. Our results demonstrate that TGF-beta1 is a potent regulator of pro-inflammatory responses and defensive reactions in dentin-pulp complex.


Communication between the Ligand-Binding Pocket and the Activation Function-2 Domain of Androgen Receptor Revealed by Molecular Dynamics Simulations.
Androgen receptor (AR), as a member of the nuclear receptor (NR) superfamily, regulates the gene transcription in response to the sequential binding of diverse agonists and coactivators. Great progress has been made in studies on the pharmacology and structure of AR, but the atomic level mechanism of the bidirectional communications between the ligand-binding pocket (LBP) and the activation function-2 (AF2) region of AR remains poorly understood. Therefore, in this study, molecular dynamics (MD) simulations and free energy calculations were carried out to explore the interactions among water, agonist (DHT) or antagonist (HFT), AR, and coactivator (SRC3). Upon the binding of an agonist (DHT) or antagonist (HFT), the LBP structure would transform to the agonistic or antagonistic state, and the conformational changes of the LBP would regulate the structure of the AF2 surface. As a result, the binding of the androgen DHT could promote the recruitment of the coactivator SRC3 to the AF2, and on the contrary, the binding of the antagonist HFT would induce a perturbation to the shape of the AF2 and then weaken its accommodating capability of the coactivators with the LXXLL motif. The simulation results illustrated that the DHT-AR binding affinity was enhanced by the association of the coactivator SRC3, which would reduce the conformational fluctuation of the AR-LBD and expand the size of the AR LBP. On the other hand, the coactivator-to-HFT allosteric pathway, which involves the SRC3, helix 3 (H3), helix 4 (H4), the loop (L1-3) between helix 1 (H1) and H3, and HFT, was characterized. The HFT's skewness and different interactions between HFT and the LBP were observed in the SRC3-present AR. The mutual communications between the AF2 surface and LBP, together with the processes involving the interplay of the ligand binding and coactivator recruitment events, would help in understanding the association of coactivators and rationally develop potent drugs to inhibit the activity of AR.


The comparative, long-term effect of the Salter osteotomy and Pemberton acetabuloplasty on pelvic height, scoliosis and functional outcome.
This study compared the long-term results following Salter osteotomy and Pemberton acetabuloplasty in children with developmental dysplasia of the hip (DDH). We assessed if there was a greater increase in pelvic height following the Salter osteotomy, and if this had a continued effect on pelvic tilt, lumbar curvature or functional outcomes. We reviewed 42 children at more than ten years post-operatively following a unilateral Salter osteotomy or Pemberton acetabuloplasty. We measured the increase in pelvic height and the iliac crest tilt and sacral tilt at the most recent review and at an earlier review point in the first decade of follow-up. We measured the lumbar Cobb angle and the Short Form-36 (SF-36) and Harris hip scores were collected at the most recent review. During the first decade of follow-up, there was a greater increase in pelvic height in the children who had a Salter osteotomy (Salter, 10.1%; Pemberton, 4.3%, p < 0.001). The difference in the increase in pelvic height was insignificant at the most recent review (Salter, 4.4%; Pemberton, 3.1%, p = 0.249). There was no significant difference between the two groups for the lumbar Cobb angle, (Salter, 3.1°; Pemberton, 3.3°, p = 0.906). A coronal lumbar curve was seen in 41 children (97%), 30 of these had a compensatory curve. Sacral tilt was the radiographic parameter for pelvic imbalance that correlated most with the lumbar Cobb angle (Pearson correlation co-efficient 0.59). The Harris hip score and SF-36 were good and showed no differences between the two groups. In the long-term, we found no difference in the functional results or pelvic imbalance between Salter osteotomy and Pemberton acetabuloplasty in the management of children with DDH. Cite this article: Bone Joint J 2016;98-B:1145-50.


Reversible multifocal leukoencephalopathy associated with a nocturnal blood pressure non-dipper pattern.
The majority of cases of leukoencephalopathy related to hypertensive crisis show brain lesions predominantly in the posterior lobe. Such cases are usually classified as reversible posterior leukoencephalopathy syndrome (RPLS). A multifocal distribution pattern is also possible, but occurs seldom. Here we report two patients with extensive white matter lesions that affect the entire brain, related to hypertensive crisis associated with a non-dipper pattern of blood pressure during the night as well as renal dysfunction. This nocturnal blood pressure abnormality may be relevant for the distribution pattern of cerebral white matter lesions and underlines the concept that in these cases a 24-h ambulatory blood pressure monitoring is needed.


Chiral resolution and binding study of 1,3,4,14b-tetrahydro-2,10-dimethyl-2H,10H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzotriazepine (10-methyl-10-azaaptazepine) and 2-methyl-1,3,4,14b-tetrahydro-2H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzothiadiazepine 10,10-dioxide (tiaaptazepine).
The affinities of the enantiomers of 1,3,4,14b-tetrahydro-2,10-dimethyl-2H,10H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzotriazepine (10-methyl-10-azaaptazepine, 5) and 2-methyl-1,3,4,14b-tetrahydro-2H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzothiadiazepine 10,10-dioxide (tiaaptazepine, 6) were evaluated in receptor binding assays. Compound (+)-(S)-5, the most significant tested enantiomer, showed good affinities for 5-HT1A, 5-HT2A 5-HT2C and alpha2NA receptors, moderate affinities for DA1, DA3r and 5-HT3 receptors and it was devoid of affinity for DA2, alpha(1NA) and muscarinic receptors. Compound (+)-(S)-5 showed an interesting pharmacological profile different from those of the reference compounds mirtazepine, mianserin and 6-methoxymianserin.


[Rehabilitation program in patients with moderate-to-severe intermittent claudication: immediate results and one year follow-up].
Physical training is believed the primary treatment of claudication symptoms. Although exercise therapy is self-effective, some drugs improving functional capacity have additive effects. TASC (Trans Atlantic Society Consensus) considers Propionil-L-Carnitine (PLC) and prostaglandin-E1 (PGE1) as poorly studied drugs with potential benefits in improving claudication. This retrospective, observational study was performed to compare the efficacy of PGE1 and PLC, and to evaluate both the immediate results of an intensive, short-course rehabilitation program and the outcome at one year follow-up. Twenty-five patients with severe-moderate claudication were selected. All patients were subjected to an intensive, supervised exercise program for 4 weeks in combination with either PGE1 (10 patients) or PLC (15 patients). Drugs were infused i.v. before every exercise session: 60 microg PGE1 within 2 hours and 600 mg PLC within 10 minutes. Patients were trained with the same supervised tread-mill walking-exercise program. At the end of the rehabilitation period, patients were instructed to keep walking (advised home exercise). Initial claudication distance (ICD) and absolute claudication distance (ACD) were evaluated during a constant treadmill test (3 km/hour speed, 10% grade) at entry, after 4 weeks and at one year follow-up. A patient was considered as no-responder if his/her improvement in ACD was <33%. A significant increase of both ICD and ACD was detected after both 4 weeks (+269% and +135%, respectively, in PGE1 group; +245% and +125%, respectively, in PLC group) and one year (+364% and +202%, respectively, in PGE1 group; +279% and +176%, respectively, in PLC group). No-responder patients after the intensive training period (2 in PGE1 group and 4 in PLC group) remained no-responders also at one year follow-up. Both PGE1 and PLC treatments were well tolerated. No serious drug-related side effect requiring interruption of the treatment was observed. A short-course of intensive exercise treatment plus PLC or PGE1 may enhance walking ability. The result was confirmed at one year follow-up.


Does plastic suture deformation induce gapping after tendon repair? A biomechanical comparison of different suture materials.
Plastic deformation of sutures creates an irreversible extension during load. To test our hypothesis that such plastic deformation causes gap formation after tendon repair, we determined the plasticity of five different suture materials commonly used in tendon surgery. Prolene, Polydioxanone (PDS), Ethibond, Vicryl, and FiberWire sutures were biomechanically tested to determine their offset yield strength, initial extension, creep, relaxed elongation, peak-to-peak displacement, stiffness, and maximum tensile strength under static, constant, and cyclic loading. In addition, 35 porcine hindlimb tendons were used to evaluate gap formation and the biomechanical behavior of the suture materials after tendon repair. Prolene had a low offset yield strength and high initial extensions at 30, 60, and 90N combined with relatively large creep, relaxed elongation, and peak-to-peak displacement. Aside from the low maximum tensile strength and stiffness, these parameters indicate an early plastic deformation during loading. The material properties of PDS were generally better for suturing than those of Prolene, but no difference was found in offset yield strength or initial extension. In contrast to the monofilament materials Prolene and PDS, the braided Ethibond, Vicryl, and FiberWire materials showed significantly less plastic deformation. The lowest amount of plastic deformation was found in the FiberWire and the results for Ethibond and Vicryl were equal. Gap formation occurred at the lowest tension force in the Prolene group, but only FiberWire required a significantly larger tension force to produce gapping at the repair site, indicating a higher resistance to gap formation. The results of this study show that plastic deformation occurs at a lower tension force in the monofilament sutures Prolene and PDS than in the braided materials Ethibond, Vicryl, and FiberWire. After tendon repair, FiberWire likely prevents gap formation, whereas Prolene induces gapping through low-tension plastic deformation. Therefore, plastic deformation should be considered when selecting suture materials for tendon repair surgery.