Multidisciplinary rehabilitation after primary brain tumour treatment.
Brain tumours can cause significant disability, which may be amenable to multidisciplinary rehabilitation. However, the evidence base for this is unclear. To assess the effectiveness of multidisciplinary rehabilitation in adults after primary brain tumour treatment, especially the types of approaches that are effective (settings, intensity) and the outcomes that are affected. We searched the Cochrane Neuromuscular Disease Group Specialized Register (March week 2, 2012), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 3, 2012), MEDLINE (1966 to March week 2, 2012), EMBASE (1980 to March week 2, 2012), PEDro (1982 to March 2012) and LILACS (1982 to March week 2, 2012). We checked the bibliographies of papers identified and contacted the authors and known experts in the field to seek published and unpublished trials. Controlled clinical trials (randomised and non-randomised clinical trials) that compared multidisciplinary rehabilitation in primary brain tumour with either routinely available local services or lower levels of intervention, or studies that compared multidisciplinary rehabilitation in different settings or at different levels of intensity. Three review authors independently assessed study quality, extracted data and performed a 'best evidence' synthesis based on methodological quality. No randomised controlled trials (RCTs) or controlled clinical trials (CCTs) were identified. No RCTs or CCTs were available for synthesis of 'best evidence' for multidisciplinary rehabilitation after treatment for brain tumour patients. However, this does not suggest the ineffectiveness of multidisciplinary rehabilitation but rather highlights the challenges in trial design and rigour, outcome measurement and complexities of care in this population. For completeness of literature, 12 observational studies (with high risk of bias) involving patients with brain tumours were included. These studies provided 'very low level' evidence suggesting that multidisciplinary rehabilitation (inpatient, home-based) may improve functional outcomes, and ambulatory programmes (outpatient and home-based) may improve vocation and quality of life. These conclusions are tentative at best, given gaps in current research in this area. Further research is needed into appropriate and robust study designs, outcome measurement, caregiver needs, evaluation of optimal settings, type, intensity, duration of therapy, and cost-effectiveness of multidisciplinary rehabilitation in the brain tumour population.


Keratinocytes and neutrophils are important sources of proinflammatory molecules in hidradenitis suppurativa.
The pathogenesis of the chronic inflammatory skin disease hidradenitis suppurativa (HS, also known as acne inversa) involves epidermal alterations such as psoriasiform epidermal hyperplasia and keratin plugging. Keratinocytes are an important source of proinflammatory molecules in inflammatory skin diseases and can be stimulated by interleukin (IL)-17(+) cells. To explore the possible role of the epithelium in the pathogenesis of HS. We performed immunohistochemical stainings and Western blot experiments to investigate the localization and expression of inflammation-associated molecules, including the cytokine IL-17, components of the inflammasome including caspase-1, and the endogenous danger-associated molecular pattern molecules S100A8 and S100A9 (calprotectin). To examine a possible effect of upregulated proinflammatory cytokines on the inflammatory infiltrate, differences in the cellular composition of perifollicular and deep dermal infiltrates were analysed. The number of IL-17(+) cells is increased in lesional and perilesional HS skin. The epidermis produces proinflammatory molecules and shows an upregulated expression of components of the NLRP3 inflammasome, activated caspase-1 and expression of S100A8/S100A9. Additionally, the course of the inflammatory process in HS involves influx of innate immune cells, particularly IL-17-expressing neutrophils. IL-17-producing cells are present in lesional and perilesional HS skin and may contribute to the initiation of inflammatory processes. Furthermore, the epidermis is a source of proinflammatory cytokines, shows inflammasome activation and expresses S100A8/S100A9, thereby possibly contributing to the propagation of inflammation. A massive influx of IL-17-expressing neutrophils is observed in the deep infiltrate.


Common femoral artery injury by blunt trauma: a case report.
Blunt injury to the common femoral artery with associated extensive soft tissue damage presented significant problems in arterial reconstruction as exemplified in this case report. Arterial restoration resolved into three phases. Initially, the femoral artery was replaced with an ipsilateral saphenous vein graft; in the second phase for septic complications, an axillofemoral bypass graft was used; and in the third phase, the contralateral saphenous vein graft was placed sequentially from the common iliac to the deep femoral to the superficial femoral to the popliteal artery. The contralateral saphenous vein had been placed in an arterialized circuit for 9 months before its harvest by means of a distal arteriovenous fistula. The primary consideration was to enlarge the small vein to approximate the caliber of the external iliac and common femoral artery. Of secondary concern was the potential for delayed aneurysmal degeneration as reported incidence in much higher in younger patients. Whether in situ arterialization influences this outcome is yet to be documented. At 36 months the saphenous vein graft is palpably normal and the ankle-brachial index is 1.0.


Clinical and pathological characteristics of metastatic tumors to the urinary bladder.
Metastatic carcinoma to the urinary bladder is a rare and under-recognized condition in surgical pathology. In this study, we identified 8 cases of true bladder metastasis at our institution in the past 20 years, excluding secondary tumors via direct extension or serosal implantation. The most common tumor type is malignant melanoma (3/8), followed by clear cell renal cell carcinoma (2/8), adenocarcinoma of the gastrointestinal tract (2/8), and breast invasive lobular carcinoma (1/8). There are 6 cases of endoscopically exophytic metastasis and 2 cases of diffuse metastasis, commensurate with 6 patients with hematuria and 2 patients with urinary obstruction as respective clinical symptoms. Exophytic bladder metastasis usually presents with similar clinical features as urothelial carcinoma, while diffuse metastasis often masquerades as a urinary tract infection. In the latter circumstance, a markedly thickened bladder wall discerned via imaging study is the best indication for the bladder biopsy to circumvent the misdiagnosis. Histologically, the metastatic tumors can also mimic conventional urothelial carcinoma or its histological variants, and thus pose a potential diagnostic challenge to pathologists. The lack of an in situ component in primary bladder cancer may hint at bladder metastasis. Accurate diagnosis of bladder metastasis requires heightened alertness to this rare condition in addition to a multidisciplinary approach.


Evaluation of bivalent vaccines candidates among VAA, OmpK and OmpR from Vibrio anguillarum in flounder (Paralichthys olivaceus).
Outer membrane protein (Omp) K, OmpR and VAA have been identified with good immunogenicity from Vibrio anguillarum, and their recombinant proteins showed variable relative percent survival (RPS) in previous study. In order to develop effective bivalent vaccine candidates, recombinant (r) VAA + rOmpK (AK), rVAA + rOmpR (AR), rOmpK + rOmpR (KR) among VAA, OmpK and OmpR, or formalin-killed cells (FKC) of V. anguillarum were immunized in flounder, respectively. Results revealed that AK, AR, KR and FKC could induce the proliferation of surface membrane immunoglobulin-positive B lymphocytes or CD3+ T lymphocytes in peripheral blood lymphocytes, and significantly enhance the total antibodies, specific antibodies and immune-related gene than those of control group. AK, AR, KR or FKC showed RPS of 74.92%, 78.49%, 82.09% and 56.99%, respectively. These results indicated that three bivalent vaccines AK, AR and KR could induce strong cellular and humoral immunity, and had high protection against V. anguillarum infection in flounders.


Depression in children and adolescents: new data on 'undertreatment' and a literature review on the efficacy of available treatments.
This article reports on the treatment received by 38 adolescents during an episode of major depression which had a median duration of 4 months. The one subject who received any pharmacologic treatment was prescribed an antianxiety agent. Sixteen percent received psychotherapy. These results are consistent with evidence from studies of adults indicating that depression is underrecognized and undertreated. An important caveat is that the small sample size limits the generalizability of these findings. Moreover, which medication should be prescribed when a diagnosis of depression is made is not yet known with certainty, as literature reviews indicate that more controlled trials of psychotherapeutic and psychopharmacologic treatments for adolescents with depression are needed to better understand the efficacy of treating depressed adolescents.


Incorporating Public Health Competencies into Veterinary Medical Education.
This study evaluates the success of secondary public health education in enhancing a professional degree in veterinary medicine. Dual-degree programs promote multidisciplinary skill attainment crucial to succeed in today's One Health-centered veterinary workforce. Participant demographics were collected including academic background, dual-degree enrollment status, and intended course of study. Survey data were collected from both Master of Public Health students and dual Doctor of Veterinary Medicine/Master of Public Health students. To measure knowledge attainment, students over a 10-year period were provided core competency and program perception-based surveys upon entering and exiting the public health program. Participants were asked to rate their knowledge of competencies based on a scale of having "no knowledge" to being "very knowledgeable." Program perceptions were reported through multiple response types. Open-ended response questions evaluated participants' perceived program success in aiding the development of professional veterinary public health knowledge. The dual nature of this degree program is hypothesized to enhance interprofessional capabilities for those entering the field of veterinary medicine. A qualitative thematic comparison of participants' entrance and exit survey responses indicated increased levels of concern for career preparation services in dual-degree students. By coursework completion, students' most valued competencies were related to epidemiology, biostatistics, and behavioral health. Quantitative analysis revealed that students concurrently enrolled in a veterinary and public health program demonstrate significantly higher levels of self-reported knowledge relating to disease measurement, ethical and legal principles, and epidemiological data interpretation. Students with educational backgrounds in veterinary and animal sciences demonstrated significantly higher levels of program satisfaction.


Protective effect of curcumin against cardiac dysfunction in sepsis rats.
The heart is one of the target organs susceptible to attack by sepsis, and protection of the cardiac function in sepsis or alleviation dysfunction caused by sepsis appears a serious and urgent problem. This study was designed to explore the effect of curcumin on myocardial injury induced by sepsis and to explore the therapeutic effect of curcumin in managing sepsis induced cardiac dysfunction. Cecal ligation and puncture surgery were used to establish the sepsis model. Curcumin was administered by peritoneal injection (200 mg/kg/d, 3 days). The effects of curcumin on the cardiac functions [Ejection Fraction (EF), Fractional Shortening (FS), Cardiac Output (CO), Heart Rate (HR)], body temperature, cTn I and superoxide dismutase levels, malondialdehyde content (an index of lipid peroxidation), and myocardial histopathological and ultrastructural studies were carried out. We demonstrated that treatment of rats with curcumin significantly decreased elevated levels of cTn I and MDA (p < 0.05) in plasma, and increase the levels of SOD (p < 0.05) after CLP. Moreover, curcumin markedly enhanced the myocardial contractility by increasing the decreased EF and FS in rats with sepsis induced by CLP (p < 0.05). In addition, curcumin could alleviate the myocardial inflammation and structure damage of myocardial cells in sepsis induced by CLP. In conclusion, the results from the present study demonstrate that curcumin has the protective effects on cardiac function in rats with sepsis and curcumin could be considered as an effective and safe therapeutic agent for the management of sepsis induced cardiac dysfunction.


Enhanced Photocarrier Generation with Selectable Wavelengths by M-Decorated-CuInS2 Nanocrystals (M = Au and Pt) Synthesized in a Single Surfactant Process on MoS2 Bilayers.
A facile approach for the synthesis of Au- and Pt-decorated CuInS2 nanocrystals (CIS NCs) as sensitizer materials on the top of MoS2 bilayers is demonstrated. A single surfactant (oleylamine) is used to prepare such heterostructured noble metal decorated CIS NCs from the pristine CIS. Such a feasible way to synthesize heterostructured noble metal decorated CIS NCs from the single surfactant can stimulate the development of the functionalized heterostructured NCs in large scale for practical applications such as solar cells and photodetectors. Photodetectors based on MoS2 bilayers with the synthesized nanocrystals display enhanced photocurrent, almost 20-40 times higher responsivity and the On/Off ratio is enlarged one order of magnitude compared with the pristine MoS2 bilayers-based photodetectors. Remarkably, by using Pt- or Au-decorated CIS NCs, the photocurrent enhancement of MoS2 photodetectors can be tuned between blue (405 nm) to green (532 nm). The strategy described here acts as a perspective to significantly improve the performance of MoS2 -based photodetectors with the controllable absorption wavelengths in the visible light range, showing the feasibility of the possible color detection.


An overview of the DSM-5: changes, controversy, and implications for psychiatric nursing.
Scheduled for publication in May 2013, the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), will guide clinical diagnoses, treatment plans, medication choices and protocols, insurance reimbursements, and research agendas throughout the United States. It will also serve as a reference manual for clinicians around the world. This primary diagnostic source used by psychiatric and mental health providers is undergoing significant change in organization and content relative to the previous edition. This article provides a general overview of what to expect in the DSM-5, highlighting major aspects of the revision. Included is a list of the proposed diagnostic categories and an overview of some of the debate and discussion accompanying the changes. Implications for psychiatric nurses and psychiatric nursing are presented.


How might pregnancy immunize against breast cancer?
This study investigated how pregnancy might protect against breast cancer. A critical review of the literature was done. Support for an active role in pregnancy immunizing against breast cancer comes from case studies demonstrating a reciprocal correlation between pregnancy and breast cancer as well as recent experiments supporting the fetal antigen hypothesis that confirms the presence of a tumor-specific antigen, MUC1, on both fetal and breast cancer tissues. Multiparous women also generate anti-MUC1 major histocompatibility complex-restricted cytotoxic T cell cytolytic activity against MUC1-bearing tumor cell lines. Careful investigation of the fetal antigen hypothesis and tolerogenic mechanisms may lead to effective vaccination protocols against breast cancer and other cancers.


[Sepsis : particularities in the elderly patients].
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection. The clinical presentation of sepsis in the elderly is very variable and sepsis is therefore challenging to diagnose in this population. The new sepsis definitions published in 2016, which are based on objective clinical and biological scores, should lead to earlier recognition and diagnosis. Treatment should start as soon as possible because the specific pathophysiological changes of aging increase the risk of a sudden deterioration to septic shock. Physicians should treat elderly patients with sepsis according to internationally recommended guidelines but should take into account specific aspects related to the elderly. These aspects include the presence of specific comorbidities and the need to clarify the overall objectives of care when deciding to admit a patient to the intensive care unit.


Strong Electronic Orbit Coupling between Cobalt and Single-Atom Praseodymium for Boosted Nitrous Oxide Decomposition on Co3O4 Catalyst.
Nitrous oxide (N2O) has gained increasing attention as an important noncarbon dioxide greenhouse gas, and catalytic decomposition is an effective method of reducing its emissions. Here, Co3O4 was synthesized by the sol-gel method and single-atom Pr was confined in its matrix to improve the N2O decomposition performance. It was observed that the reaction rate varied in a volcano-like pattern with the amount of doped Pr. A N2O decomposition reaction rate 5-7.5 times greater than that of pure Co3O4 is achieved on the catalyst with a Pr/Co molar ratio of 0.06:1, and further Pr doping reduced the activity due to PrOx cluster formation. Combined with X-ray photoelectron spectroscopy, X-ray absorption fine structure, density functional theory and in situ near-ambient pressure X-ray photoelectron spectroscopy, it was demonstrated that the single-atom doped Pr in Co3O4 generates the "Pr 4f-O 2p-Co 3d" network, which redistributes the electrons in Co3O4 lattice and increases the t2g electrons at the tetracoordinated Co2+ sites. This coupling between the Pr 4f orbit and Co2+ 3d orbit triggers the formation of a 4f-3d electronic ladder, which accelerates the electron transfer from Co2+ to the 3π* antibonding orbital of N2O, thus contributing to the N-O bond cleavage. Moreover, the energy barrier for each elementary reaction in the decomposition process of N2O is reduced, especially for O2 desorption. Our work provides a theoretical grounding and reference for designing atomically modified catalysts for N2O decomposition.


Isokite, CaMg(PO(4))F(0.8)(OH)(0.2), isomorphous with titanite.
This study presents the first structural report of natural isokite (calcium magnesium phosphate fluoride), with the formula CaMg(PO(4))F(0.8)(OH)(0.2) (i.e. some substitution of OH for F), based on single-crystal X-ray diffraction data. Isokite belongs to the C2/c titanite mineral group, in which Mg is on an inversion centre and the Ca, P and F/OH atoms are on twofold axes. The structure is composed of kinked chains of corner-sharing MgO(4)F(2) octahedra that are crosslinked by isolated PO(4) tetrahedra, forming a three-dimensional polyhedral network. The Ca(2+) cations occupy the interstitial sites coordinated by six O atoms and one F anion.


Post-traumatic Ruptured Scrotal Collection: Pyocele or Hematocele?
Ultrasound is the modality of choice for detecting the causes of acute scrotal pain and diagnosing scrotal pathologies. Pyocele is a term used for describing the purulent fluid collection in the scrotal sac, which may present to the hospital as a complication of testicular abscess, epididymal-orchitis, or post-trauma. Ultrasound is the modality of choice for diagnosing such pathologies. The presented case is of a young male from rural India who developed a pyocele post-trauma and underwent an ultrasound examination, where it was found to be a ruptured pyocele with contents spreading into the hemi-scrotum. Rupture of the tunica is frequently associated with the hematocele; however, pyocele is less commonly associated with rupture. The case report discusses the causes of pyocele, imaging features, management, and complications of this pathology along with other possible differential diagnosis.


[Choosing treatment for patients with bladder cancer combined with prostatic hyperplasia].
To define treatment selection criteria for patients with bladder cancer combined with benign prostatic hyperplasia (BPH). Between 2006 and 2015, 1148 patients were treated for bladder cancer and 3368 patients for BPH. Among them, 258 (22.5%) patients had both bladder cancer and BPH. 113 (11.6%) patients had indications for surgical treatment of both diseases. In this group, 18 (13.5%) patients also had bladder stones. Only 2 (1.6%) patients had tumor invading the muscle wall, while the remaining patients had non-muscle invasive bladder cancer. In 18% of patients the surgery was done in two stages, the first for bladder cancer and the second for BPH. The remaining 82% of patients underwent simultaneous surgery. Bladder cancer recurred in 34.4% of patients. Comparative evaluation of the results of transurethral resection of the bladder and prostate showed a greater number of intraoperative complications in patients who underwent staged surgery. In our opinion, it may be attributed to the lack of adequate visualization and access to the tumor, located near the opening of the ureter, to the intravesical prostate growth or large median lobe of the prostate. Bladder tumors greater than 3 cm, the multiple lesions and the low tumor differentiation were associated with a higher risk of bladder cancer recurrence, but recurrence rates of simultaneous and staged surgeries were not significantly different. The treatment of patients with bladder cancer in combination with BPH and bladder stones depended on the prostate volume, the number and size of stones. To reduce the risk of complications, in cases with assumed operating time more than 2 hours, it is advisable to split the treatment into two stages with BPH surgery on the second stage.


Methods for the isolation of Aeromonas hydrophila and Plesiomonas shigelloides from faeces.
Two solid selective media, xylose deoxycholate citrate agar (XDCA) and bile salts brilliant green agar (BBG) and an enrichment broth-alkaline peptone water, were evaluated for the isolation of Aeromonas hydrophila and Plesiomonas shigelloides. Alkaline peptone water and XDCA are useful for recovery of Aeromonas but not Plesiomonas, whereas BBG is satisfactory for both organisms.


[Genetic counselling: theoretical aspects and prenatal practice].
Genetic counselling provides families with accurate medical information and psychological support. Respect and concern for the emotional well-being should be taken into account while discussing genetics aspects and recurrence risks. The importance of autonomy and confidentiality, central to genetic counselling, is reinforced by the new Swiss law (LAGH). In many countries, most of the genetic counselling is provided by genetic counsellors who have a specialised post-graduate training. Genetic counselling plays an increasing role in different medical specialities. In particular, it is essential in the context of prenatal and pre-conceptual care, where couples are confronted to complex information and should have access to appropriate support during the decision-making process.


The Activity of Chemotherapy in Inflammatory Myofibroblastic Tumors: A Multicenter, European Retrospective Case Series Analysis.
This study aimed to review the activity of cytotoxic chemotherapy in patients with inflammatory myofibroblastic tumors (IMTs) treated at nine European sarcoma reference centers. Patients of any age, with histologically proven IMT, treated with anthracycline-based methotrexate plus/minus vinorelbine/vinblastine (MTX-V) or other chemotherapeutic regimens between 1996 and 2018 were retrospectively reviewed. Diagnosis was confirmed at the local level by an expert pathologist. Response was retrospectively assessed by local investigators by RECIST v1.1. Progression-free survival (PFS), relapse-free survival (RFS), and overall survival (OS) were computed by Kaplan-Meier method. Thirty-eight patients were included. Twenty-five patients (8 localized, 17 advanced disease) received an anthracycline-based regimen; 21 were evaluable for response. Overall response rate (ORR) was 10/21 (47.6%). At a 70.8-month median follow-up (FU), median RFS and median OS were not reached (NR) in patients with localized disease; median PFS and median OS were 6.3 (interquartile range [IQR]: 1.9-13.4) and 21.2 (IQR: 7.7-40.7) months in patients with advanced disease. Thirteen patients received MTX-V (4 localized, 9 advanced disease), all evaluable for response. ORR was 7/13 (53.8%). At a 56.6-month median FU, median RFS and median OS were 42.5 (IQR: 12.9-61.2) months and NR (no death events) in patients with localized disease, and NR (IQR: 24.9 to NR) and 83.4 months (IQR: 83.4 to NR) in patients with advanced disease. In the "other-regimens group," responses were seen in 3/4 patients treated with oral cyclophosphamide and 1/2 with docetaxel/gemcitabine. Anthracycline-based and MTX-V regimens are very effective in IMT, with a similar ORR in both groups. MTX-V achieved a prolonged disease control. Responses were also seen with oral cyclophosphamide and docetaxel/gemcitabine, but few patients were treated with these schedules. Inflammatory myofibroblastic tumor (IMT) is an ultrarare sarcoma with known sensitivity to anaplastic lymphoma kinase (ALK) inhibitors in ALK-fused cases, although ALK inhibitors are not licensed in the disease. The current knowledge on the activity of cytotoxic chemotherapy is limited. This multi-institutional retrospective study on pediatric and adult patients with IMT shows that cytotoxic chemotherapy, and in particular anthracycline-based and methotrexate plus/minus vinorelbine/vinblastine regimens, represents a treatment option and can be considered in IMT patients irrespectively from ALK status. This study provides a benchmark for future studies on new medical therapies.


A case of Mycoplasma pneumoniae-associated encephalomyelitis in a 16-year-old female presenting to an adult teaching hospital.
We report a rare cause of encephalitis that is not often described in the adult clinical setting. Our case was a 16-year-old female who presented with a clinical picture of viral encephalitis; however, magnetic resonance imaging showed a demyelinating lesion of the left frontal lobe. In this age group, differential diagnoses of acute demyelination encephalomyelitis and multiple sclerosis were entertained. Further investigations demonstrated positive Mycoplasma pneumoniae serology. As a result, a diagnosis of Mycoplasma pneumoniae-associated encephalitis was made based on a process of exclusion.


Yolk vitamin E prevents oxidative damage in gull hatchlings.
Oxidative stress experienced during early development can negatively affect diverse life-history traits, and organisms have evolved complex defence systems against its detrimental effects. Bird eggs contain maternally derived exogenous antioxidants that play a major role in embryo protection from oxidative damage, including the negative effects on telomere dynamics. In this study on the yellow-legged gull (Larus michahellis), we manipulated the concentration of vitamin E (VE) in the egg yolk and analysed the consequences on oxidative status markers and telomere length in the hatchlings. This study provides the first experimental evidence that, contrary to the expectation, a physiological increase in yolk VE concentration boosted total antioxidant capacity and reduced the concentration of pro-oxidant molecules in the plasma, but did not reduce telomere attrition or ameliorate oxidative damage to proteins and lipids in the early postnatal period.


Staining of colloid bodies by keratin antisera in lichen planus.
Immune sera against total keratin, as well as three keratin polypeptide subunits, were raised in guinea pig with different bands of stratum corneum fibrous proteins derived from normal human epidermis and isolated by SDS polyacrylamide gel electrophoresis. The staining pattern of the different polypeptide antisera using the indirect immunofluorescence and immunoperoxidase methods in biopsy specimens of normal human epidermis confirmed recently published results. Biopsy specimens from 10 lesions of lichen planus were studied by indirect immunofluorescence and immunoperoxidase methods utilizing the same four different specific antikeratin immune sera. Most often the staining pattern with the different immune sera was similar to that seen in normal keratinized epidermis. In all specimens, intense staining of the colloid bodies was detected with the different immune sera. This finding favors the concept that colloid bodies originate from keratin filaments. Control staining with pre-immune serum was always negative. In one case of bullous lichen planus, colloid bodies were not labeled by 67 K and 62 K immune sera, but were intensely stained with 55 K and total keratin antisera. Moreover, with 55 K immune serum there was more intense staining of certain basal cells. The correlation between these findings and previously published studies by electron microscopy is discussed.


Metabolic profiling of maternal serum of women at high-risk of spontaneous preterm birth using NMR and MGWAS approach.
Preterm birth (PTB) is a leading global cause of infant mortality. Risk factors include genetics, lifestyle choices and infection. Understanding the mechanism of PTB could aid the development of novel approaches to prevent PTB. This study aimed to investigate the metabolic biomarkers of PTB in early pregnancy and the association of significant metabolites with participant genotypes. Maternal sera collected at 16 and 20 weeks of gestation, from women who previously experienced PTB (high-risk) and women who did not (low-risk controls), were analysed using 1H nuclear magnetic resonance (NMR) metabolomics and genome-wide screening microarray. ANOVA and probabilistic neural network (PNN) modelling were performed on the spectral bins. Metabolomics genome-wide association (MGWAS) of the spectral bins and genotype data from the same participants was applied to determine potential metabolite-gene pathways. Phenylalanine, acetate and lactate metabolite differences between PTB cases and controls were obtained by ANOVA and PNN showed strong prediction at week 20 (AUC = 0.89). MGWAS identified several metabolite bins with strong genetic associations. Cis-eQTL analysis highlighted TRAF1 (involved in the inflammatory pathway) local to a non-coding SNP associated with lactate at week 20 of gestation. MGWAS of a well-defined cohort of participants highlighted a lactate-TRAF1 relationship that could potentially contribute to PTB.


Pediatric palliative care communication: resources for the clinical nurse specialist.
The purpose of this article was to highlight the lack of communication skills pediatric practitioners have when delivering bad news and introducing pediatric palliative care to a family with a child with a life-limiting condition. Fortunately, innovative tools and guidelines have been appearing in recent literature, and the clinical nurse specialist has an opportunity to implement these communication tools by utilizing her core competencies. Over 10 years ago, the American Academy of Pediatrics and the World Health Organization individually prepared definitions and mandates concerning the importance of pediatric palliative care. Approximately 450,000 children are currently living at home with chronic, life-limiting health conditions, many of whom are not receiving any palliative care services. Literature about practitioner communication practices and resources was reviewed. Advances are being made in pediatric palliative research, guidelines, and clinical tools. New advances are not being disseminated to the pediatric healthcare practitioner population, leaving practitioners with inadequate education and preparation for implementing pediatric palliative care. The clinical nurse specialist has the ability to cross through the spheres of influence by providing holistic care, implementing system changes, and by using a communication framework when working with palliative care patients and families.


Complexes of copper(I) and silver(I) with bis(methimazolyl)borate and dihydrobis(2-mercaptothiazolyl)borate ligands.
The complexes [Cu(BmMe)]3 x 0.77C4H8O (1), [(BmMe)Ag(PPh3)] (2) and [M[kappa3-H(micro-H)B(tiaz)2](PPh3)] (M= Cu (3), Ag (4); BmMe = bis(2-mercapto-1-methylimidazolyl)borate, H2B(tiaz)2 = dihydrobis(2-mercaptothiazolyl)borate) have been prepared and characterised by X-ray crystallographic and spectroscopic methods. The presence of MH-B interactions in these species has been investigated using infrared spectroscopy and crystallography. In [Cu(BmMe)]3, the triangular array of three trigonal-planar copper atoms is coordinated by three chelating and bridging (BmMe)- ligands, and has an unusual, highly unsymmetrical arrangement with one short Cu-Cu distance; this is the first structurally authenticated Bm(Me) complex with a nuclearity greater than two. In complexes 2-4, the metal atom is found in a distorted trigonal-planar geometry, bound by a terminal phosphine ligand and two sulfur atoms of a chelating ligand, supplemented by an MH-B interaction, which appears to be a common feature in the coordination chemistry of the (BmMe)- and [H2B(tiaz)2]- ligands; compounds 1-4 are the first reported complexes of copper(I) and silver(I) with any bis(2-mercaptoimidazolyl)borate ligand or with H2B(tiaz)2.


How multiple types of stressors impact on health.
Although many studies have focused on the relationship between stress and health, few have examined the impact of multiple types of stressors. The current study investigated the health impact of four stressors: sexual and physical abuse history, lifetime losses and traumas, turmoil in childhood family, and recent stressful life events. The sample included 239 female patients from a referral-based gastroenterology clinic. We found that the four stressors (abuse history, lifetime traumas, turmoil in childhood family, and recent stressful life events) were related to poor health status (eg, more pain, symptoms, bed disability days, physician visits, functional disability, and psychological distress); together, these stressors accounted for 32% of the variance in overall current health. Furthermore, women who scored high on one type of stressor also tended to have experienced other types. Unlike many previous studies, we did not find that social support buffered the effects of stress. This study provides evidence that many different types of stressors independently contribute to poor health outcome. Such findings suggest that health practitioners and researchers should question patients about histories of traumatic events, in addition to the examination of the biological aspects of illness, inasmuch as both may have notable effects on health status.


Plasmin-mediated activation and inactivation of thrombin-activatable fibrinolysis inhibitor.
Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) attenuates the fibrin cofactor function of tissue-type plasminogen activator-mediated plasmin formation and subsequently fibrin degradation. In the present study, we focused on the role of plasmin in the regulation of TAFIa activity. Upon incubation with plasmin, TAFIa activity was generated, which was unstable at 37 degrees C. Analysis of the cleavage pattern showed that TAFI was cleaved at Arg(92), releasing the activation peptide from the 35.8-kDa catalytic domain. The presence of the 35.8-kDa fragment paralleled the time course of generation and loss of TAFIa activity. This suggested that, in the presence of plasmin, TAFIa is probably inactivated by proteolysis rather than by conformational instability. TAFI was also cleaved at Arg(302), Lys(327), and Arg(330), resulting in a approximately 44.3-kDa fragment and several smaller fragments. The 44.3-kDa fragment is no longer activatable since it lacks part of the catalytic center. We concluded that plasmin can cleave at several sites in TAFI and that this contributes to the regulation of TAFI and TAFIa.


Recruitment of underrepresented minority students to medical school: minority medical student organizations, an untapped resource.
Recruitment of more underrepresented minority students (black, Hispanic and native American) to increase racial diversity in the physician workforce is on the agenda for medical schools around the nation. The benefits of having a racially diverse class are indisputable. Minority physicians are more likely to provide care to minority, underserved, disadvantaged and low-income populations. Therefore, medical schools would benefit from diversity through utilizing strategies for recruitment of underrepresented minority (URM) students. Numerous recruitment strategies have been employed to increase the number of underrepresented minority students. However, formal collaboration with minority medical student organizations is an underutilized tool in the recruitment process. Many medical schools have informally used minority medical students and members of various minority organizations on campus in the recruitment process, but a formal collaboration which entails a strategic approach on using minority medical student organizations has yet to be included in the literature. This paper discusses the innovative collaboration between the University of Toledo College of Medicine (UTCOM) chapter of the Student National Medical Association (SNMA) and the college of medicine's admissions office to strategize a recruitment plan to increase the number of underrepresented minority students at the UTCOM. This paper suggests that minority medical student organizations, particularly the SNMA, can be used as a recruiting tool; hence, admissions offices cannot negate the usefulness of having formal involvement of minority medical student organizations as a recruiting tool. This approach may also be applicable to residency programs and other graduate professional fields with a severe shortage of URM students.


Selenium nanoparticles with low-level ionizing radiation exposure ameliorate nicotine-induced inflammatory impairment in rat kidney.
Occupational exposure to low-level ionizing radiation (<1 Gy) was shown to enhance cell protection via attenuating an established inflammatory process. Nicotine, a major toxic component of cigarette smoke, is responsible for smoking-mediated renal dysfunction. The present study was therefore aimed to investigate the protective impact of ginger Zingiber officinale selenium nanoparticles (SeNPs) with whole-body low-dose gamma radiation (γ-R) against nicotine-induced nephrotoxicity in male albino rats. Nicotine intoxication was induced with 0.5 mg/kg BW. Rats received 0.1 mg SeNPs/kg BW by gastric gavage concomitant with 0.5 Gy γ-R over 4 weeks. Characterization studies showed the formation of spherical SeNPs with a size ranged from 10 to 30 nm in diameter with a thin film encapsulating the nanoballs. Our data revealed that nicotine induced renal dysfunction manifested by significant abnormal levels of kidney function markers (creatinine, urea, sodium and potassium) accompanied by increased levels of malondialdehyde along with a reduction in glutathione level, glutathione peroxidase, and glutathione S-transferase activities. It is worthy to note that nicotine toxicity induced significant increments in serum inflammatory markers: tumor necrosis factor-α and vascular cell adhesion protein 1. Western blotting showed marked significant elevation in caspase-3 activities against nicotine. The mRNA gene expression of inducible cyclooxygenase-2 gene was highly increased with nicotine intoxication while that of cyclooxygenase-1 did not show any changes. Interestingly, our data demonstrated that SeNPs in synergistic interaction with γ-R are efficacious control against nicotine-induced nephrotoxicity via anti-oxidant-mediated anti-inflammatory activities. Thus, it is tempting to recommend dietary approaches with ginger SeNPs for smokers at workplaces exposed occupationally and regularly to low-level ionizing radiation.


2016 JOSPT Awards: Additive Effects and Biological Mechanisms of Interventions Offer Important Insights.
During the American Physical Therapy Association's Combined Sections Meeting in San Antonio, TX in February 2017, JOSPT recognized the authors of the most outstanding research and clinical practice manuscripts published in JOSPT during 2016. The 2016 JOSPT Excellence in Research Award was presented to Carol A. Courtney, Alana D. Steffen, César Fernández-de-las-Peñas, John Kim, and Samuel J. Chmell, MD, for their March 2016 article "Joint Mobilization Enhances Mechanisms of Conditioned Pain Modulation in Individuals With Osteoarthritis of the Knee." The 2016 George J. Davies-James A. Gould Excellence in Clinical Inquiry Award was presented to Seyda Toprak Celenay, Turkan Akbayrak, and Derya Ozer Kaya for their February 2016 article "A Comparison of the Effects of Stabilization Exercises Plus Manual Therapy to Those of Stabilization Exercises Alone in Patients With Nonspecific Mechanical Neck Pain: A Randomized Clinical Trial." J Orthop Sports Phys Ther 2017;47(4):225-227. doi:10.2519/jospt.2017.0104.


Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis.
Experimental validation of enzyme function is crucial for genome interpretation, but it remains challenging because it cannot be scaled up to accommodate the constant accumulation of genome sequences. We tackled this issue for the MetA and MetX enzyme families, phylogenetically unrelated families of acyl-L-homoserine transferases involved in L-methionine biosynthesis. Members of these families are prone to incorrect annotation because MetX and MetA enzymes are assumed to always use acetyl-CoA and succinyl-CoA, respectively. We determined the enzymatic activities of 100 enzymes from diverse species, and interpreted the results by structural classification of active sites based on protein structure modeling. We predict that >60% of the 10,000 sequences from these families currently present in databases are incorrectly annotated, and suggest that acetyl-CoA was originally the sole substrate of these isofunctional enzymes, which evolved to use exclusively succinyl-CoA in the most recent bacteria. We also uncovered a divergent subgroup of MetX enzymes in fungi that participate only in L-cysteine biosynthesis as O-succinyl-L-serine transferases.


Impact of random and fixed (optimal) sampling approach on the Bayesian estimation of clearance.
The population pharmacokinetic approach is based on sparse sampling. In sparse sampling approaches, the selection of the time point(s) is very critical for the prediction of pharmacokinetic parameters. Several investigators have shown that the predictive performance of the Bayesian approach is influenced by the initial estimates of pharmacokinetic parameters as well as the time of blood sampling. The objective of this study is to evaluate the impact of random and fixed sparse sampling approach on the Bayesian estimation of clearance. Three drugs were selected for this study. Two sparse sampling methods (random or fixed) using Bayesian approach were used to assess clearance in healthy subjects following a single oral dose. The initial estimates of the model parameters and inter- and intra-subject variabilities were obtained from the previous pharmacokinetic studies conducted in healthy volunteers. The predicted clearance values using sparse sampling (1, 2 or 3 blood samples per subject) were compared with the clearance values obtained by extensive sampling. The results indicated that both random and fixed sampling approaches, irrespective of number of blood samples, can be used to estimate mean population as well as post hoc predicted individual clearance (Bayesian) with accuracy. However, the precision of the prediction of clearance was found to be better with fixed rather random blood sampling approach.


Planning a continuing education program: the model for health education planning.
1. Development of CE programs for occupational health nurses is integral to professional development. Occupational health nurses are constantly being required to increase and upgrade skills. 2. Evolving issues in health care reform reflect an emphasis on the cost effective, quality care provided by well prepared occupational health nurses. Thus, the need for providing high quality programs and resources for occupational health nurses becomes a challenge for CE providers. 3. The Model for Health Education Planning (MHEP) is used to describe the development of a program. The MHEP includes six phases: initiation, needs assessment, goal setting, planning/programming, implementation, and evaluation. 4. Use of the MHEP ensures that the program planning process is achieved in an appropriate manner. The focus is on meeting the needs of the learner.


Comorbidity of Obsessive-Compulsive Disorder and Schizotypal Personality Disorder: Clinical Response and Treatment Resistance to Pharmacotherapy in a 3-Year Follow-Up Naturalistic Study.
The present study aims to analyze the clinical and socio-demographic characteristics of patients with obsessive-compulsive disorder (OCD) in comorbidity with schizotypal personality disorder (SPD), as well as the response rate to pharmacological treatments. OCD+SPD patients had a younger age at onset, a higher probability to have more severe obsessive-compulsive symptoms, a higher rate of schizophrenia spectrum disorders in their first-degree relatives, and a poorer insight compared to OCD patients. During the 3-year follow-up period, these patients showed a lower rate of recovery, thus requiring augmentation with different psychotropic medications, including low doses of antipsychotics. Our findings suggest that the comorbidity of OCD and SPD causes a poor treatment response, and a reduced probability to recover using standard pharmacological treatment strategies. Further investigations are needed to identify alternative strategies, including psychoeducation and cognitive behavioral therapy, to manage such frequent comorbidity in clinical practice.


Patient-Reported Allergies are Associated with Increased Rate of Postoperative Stiffness After Arthroscopic Rotator Cuff Repair.
Several risk factors have been identified for the development of postoperative shoulder stiffness, and there has been increasing interest in orthopedic literature regarding patient-reported allergy (PRA) as an identifiable risk factor for adverse outcomes. The purpose of this study is to determine whether PRAs are associated with subsequent rates of diagnosis of adhesive capsulitis (AC) or return to the operating room for postoperative shoulder stiffness within two years following arthroscopic rotator cuff repair (ARCR). Patients were retrospectively identified using Current Procedural Terminology surgical billing codes to identify patients who underwent ARCR at a single urban academic institution from January 2012 to December 2020 with minimum 2-year follow-up. Lysis of adhesions (LOA), MUA, and adhesive capsulitis of the shoulder were further queried within two years postoperatively for the ipsilateral shoulder. Patients were excluded if they had undergone ipsilateral MUA/LOA or received a diagnosis of AC prior to the index procedure. Demographic characteristics and medical comorbidities (hypertension, diabetes, hyperlipidemia, hypothyroidism) were extracted from electronic medical records. Baseline characteristics were compared between patients with and without PRAs. Multivariate logistic regression analyses were performed to determine the association of the presence of PRAs overall, as well as presence one, two, or three or more PRAs, with subsequent MUA/LOA or diagnosis of AC within two years postoperatively. Of 7,057 patients identified in the study period, 6,583 patients were eligible for the final analysis. The mean age was 56.6±11.7 years and the mean BMI was 29.1±5.6. Overall, 19.3% of patients (n=1,271) reported at least one allergy and 7.1% (n=469) had >1 PRA. 44 patients (0.7%) underwent subsequent ipsilateral MUA/LOA within two years postoperatively, while 93 patients (1.4%) received a diagnosis of ipsilateral AC in the same time frame. PRAs were significantly associated with subsequent diagnosis of AC (OR 2.39; 95% CI [1.45-3.92]; p<.001), but not MUA/LOA (OR 1.97, 95% CI [1.26-3.61]; p=0.133). Patients with two PRAs had greater odds of being diagnosed with AC than patients with one PRA (OR: 2.74; 95% CI [1.14-5.99]; p=0.012). While this association was non-significant for MUA/LOA, patients with 2 PRAs (OR: 2.67; 95% CI [0.96-8.80]; p=0.059) demonstrated a similar statistical trend. Patient-reported allergies are associated with increased odds of receiving a diagnosis of adhesive capsulitis within two years following arthroscopic rotator cuff repair, but were not found to be associated with return to the operating room for postoperative stiffness.


KTa0.6Nb0.4O3 ferroelectric thin film behavior at microwave frequencies for tunable applications.
In this study about the relationships between structural and microwave electrical properties of KTa(1-x)NbxO3 (KTN) ferroelectric materials, a KTN thin film was deposited on different substrates to investigate how KTN growth affects the microwave behavior. Interdigital capacitors and stubs were made on these films through a simple engraving process. Microwave measurements under a static electric field showed the importance of the substrate on the circuit behavior and, notably, on the tuning factor.


Exponential approximation for one-component Yukawa plasma.
A theory based on the exponential approximation of the liquid-state theory is applied to study properties of several models of one-component Yukawa plasma characterized by different values of the screening parameter z. The results of the new theory are compared to the results of a conventional theory, which is based on the first-order mean spherical approximation, and to the results of a Monte Carlo simulation. The new theory shows improvements in the predictions for the thermodynamic and structural properties of Yukawa plasmas with high and intermediate values of the screening parameter, z, and coupling parameter, Γ. For low values of z and Γ, the new theory is comparable in accuracy to the conventional theory, which in turn agrees well with the results of the Monte Carlo simulation.


Enabling Expedited Disposition of Emergencies Using Telepsychiatry in Israel: Protocol for a Hybrid Implementation Study.
Telepsychiatry is the use of virtual communication, such as a video link, to deliver mental health assessment, treatment, and follow-up. Previous studies have shown telepsychiatry to be feasible, accurate compared with in-person practice, and satisfying for psychiatrists and patients. Telepsychiatry has also been associated with reduced waiting times for evaluation and, in some studies, lower admission rates. However, most previous studies focused on using telepsychiatry in community settings and not on involuntary admission. The aim of this study is to examine the effectiveness and implementation process of patient assessment for involuntary admissions in the psychiatric emergency department (ED) using a video link. This type 1 hybrid implementation study will examine telepsychiatry effectiveness and the implementation process, by comparing telepsychiatry (n=240) with historical controls who had a face-to-face evaluation (n=240) during the previous, usual care period in 5 psychiatric EDs in Israel. A temporary waiver of the standing policy requiring in-person evaluations only, for the purpose of research, was obtained from the Israeli Ministry of Health. During the telepsychiatry phase, clinical staff and patients will join a video call from the ED, while the attending physician will log in elsewhere. The Promoting Action on Research Implementation in Health Services (PARIHS) framework will guide the evaluation of the telepsychiatry implementation process in the ED. PARIHS has the following 3 constructs: (1) evidence: staff's opinions regarding the innovation's viability and practicality, their satisfaction levels with its use, and patients' perceptions of the change; (2) context: level of approval of new strategies in the ED, decision-making processes, and the manner in which clinical teams converse and work together; (3) facilitation: adequacy of the facilitation efforts using champions reports. Primary clinical outcomes include ED length of stay and violent incidents obtained from medical records. This study received Helsinki approval from the Ethics Committee of Abarbanel Mental Health Center (174; March 13, 2023), Jerusalem Mental Health Center (22-21; November 6, 2022), Lev-Hasharon Mental Health Medical Center (LH12023; February 12, 2023), Tel-Aviv Medical Center (TLV-22-0656; January 3, 2023), and Sha'ar Menashe (1-4-23; April 18, 2023). Data collection began in July 2023 in 2 study sites and will begin soon at the others. Telepsychiatry could have significant benefits for patients in the psychiatric ED. Examining telepsychiatry effectiveness in the ED, in addition to identifying the facilitators and barriers of implementing it in different emergency settings, will facilitate better policy decisions regarding its implementation. ClinicalTrials.gov NCT05771545; https://clinicaltrials.gov/study/NCT05771545. DERR1-10.2196/49405.


Functional characterization of IScs605, an insertion element carried by tetracycline-resistant Chlamydia suis.
Stable tetracycline resistance in Chlamydia suis is mediated by a family of genomic islands [the tet(C) islands] that are integrated into the chlamydial chromosome. The tet(C) islands contain several plasmid-specific genes, the tet(C) resistance gene and, in most cases, a novel insertion element (IScs605) encoding two predicted transposases. The hypothesis that IScs605 mediated the integration of the tet(C) resistance islands into the C. suis genome was tested using a plasmid-based transposition system in Escherichia coli. Both high- and medium-copy-number plasmids were used as carriers of IScs605 in these experiments. IScs605 integrated into a target plasmid (pOX38) when delivered by either donor plasmid, and integration of the entire donor plasmid was common. IScs605-mediated integration occurred at many positions within pOX38, with 36 of 38 events adjacent to a 5'-TTCAA-3' sequence. Deletions in each of the candidate transposase genes within IScs605 demonstrated that only one of the two ORFs was necessary for the observed transposition activity and target specificity. Analysis of progeny from the mating assays also indicated that IScs605 can excise following integration into a target DNA, and, in each tested case, the sequence 5'-AATTCAA-3' remained at the site of excision. Collectively, these results are consistent with the nucleotide sequence data collected for the tet(C) islands, and strongly suggest that a transposase within IScs605 is responsible for integration of these genomic islands into the C. suis chromosome.


Gluconic acid production by an mobilized glucose oxidase reactor with electrochemical regeneration of an artificial electron acceptor.
A reactor, using the enzymatic electrocatalysis scheme, was developed on a laboratory preparative scale for the catalytic oxidation of glucose into gluconic acid. Glucose oxidase was directly immobilized on the surface of a carbon felt electrode and a solution of glucose and benzo-quinone passed through the electrode in order to regenerate the electron acceptor. The reactor was able to produce continuously 1.5 g gluconate/h with a catalytic current of 0.4 A. This gave a high productivity ca. 100 g/h/L reactor. A one-dimensional model was developed which demonstrated the efficiency of coupling between enzymatic and electrochemical reactions due to the proximity of the two reaction sites. For example the catalytic current was practically independent of mass transfer parameters. The operational stability of immobilized glucose oxidase was increased 50 times at least when electroregenerated benzoquinone was used as oxidant instead of oxygen.


Three patients with Schaaf-Yang syndrome exhibiting arthrogryposis and endocrinological abnormalities.
MAGEL2 is the paternally expressed gene within Prader-Willi syndrome critical region at 15q11.2. We encountered three individuals in whom truncating mutations of MAGEL2 were identified. Patients 1 and 2, siblings born to healthy, non-consanguineous Japanese parents, showed generalized hypotonia, lethargy, severe respiratory difficulty, poor feeding, and multiple anomalies including arthrogryposis soon after birth. We carried out whole-exome sequencing, which detected a MAGEL2 mutation (c.1912C>T, p.Gln638*, heterozygous). The patients' father was heterozygous for the mutation. Patient 3 was a female infant, showed respiratory difficulty reflecting pulmonary hypoplasia, generalized hypotonia, feeding difficulty and multiple anomalies soon after birth. Targeted next-generation sequencing detected a novel heterozygous mutation in MAGEL2 (c.3131C>A, p.Ser1044*). This mutation was not found in the parents. MAGEL2 mutations, first reported to be the cause of the Prader-Willi like syndrome with autism by Schaaf et al. (2013) Nature Genetics, 45: 1405-1408 show the wide range of phenotypic spectrum from lethal arthrogryposis multiplex congenital to autism spectrum disorder (ASD) and mild intellectual disability (ID). Our results indicate that MAGEL2 mutations cause multiple congenital anomalies and intellectual disability accompanied by arthrogryposis multiplex congenita and various endocrinologic abnormalities, supporting that the view that clinical phenotypes of MAGEL2 mutations are variable.


Poly[aqua(μ-vinyl-phospho-nato)cadmium].
The title compound, [Cd(C(2)H(3)O(3)P)(H(2)O)](n), was obtained from vinyl-phospho-nic acid and cadmium nitrate. The vinyl groups project into the inter-lamellar space and the structure is held together via van der Waals forces. The Cd(2+) ion is six-coordinate and the geometry is best described as distorted octa-hedral, with O-Cd-O angles falling within the range 61.72 (13)-101.82 (14)°. Five of the coordinated oxygen atoms originate from the phospho-nate group and the sixth from a bound water molecule. Cd-O distances lie between 2.220 (3) and 2.394 (2) Å. The water mol-ecule is hydrogen bonded to a phospho-nate oxygen atom.


Pretransplant MELD score and post liver transplantation survival in the UK and Ireland.
It has been shown that the model for end-stage liver disease (MELD) score is an accurate predictor of survival in patients with liver disease without transplantation. Four recent studies carried out in the United States have demonstrated that the MELD score obtained immediately prior to transplantation is also associated with post-transplant patient survival. Our aim was to evaluate how accurately the MELD score predicts 90-day post-transplant survival in adult patients with chronic liver disease in the UK and Ireland. The UK and Ireland Liver Transplant Audit has data on all liver transplants since 1994. We studied survival of 3838 adult patients after first elective liver transplantation according to United Network for Organ Sharing categories of their MELD scores (< or = 10, 11-18, 19-24, 25-35, > or =36). The overall survival at 90-days was 90.2%. The 90-day survival varied according to the United Network for Organ Sharing MELD categories (92.6%, 91.9%, 89.7%, 89.7%, and 70.8%, respectively; P < 0.01). Therefore, only those patients with a MELD score of 36 or higher (3% of the patients) had a survival that was markedly lower than the rest. As a consequence, the ability of the MELD score to discriminate between patients who were dead or alive was poor (c-statistic 0.58). Re-estimating the coefficients in the MELD regression model, even allowing for nonlinear relationships, did not improve its discriminatory ability. In conclusion, in the UK and Ireland the MELD score is significantly associated with post-transplant survival, but its predictive ability is poor. These results are in agreement with results found in the United States. Therefore, the most appropriate system to support patient selection for transplantation will be one that combines a pretransplant survival model (e.g., MELD score) with a properly developed post-transplant survival model.


Physiopathology and clinical aspects of diabetic nephropathy.
End-stage renal failure is a severe and relatively frequent complication of insulin-dependent diabetes, also representing the only growing cause of uremia requiring replacement therapy in Western countries. Five principal pathogenic factors are to be considered: genetic, immunologic, hemorheologic, biochemic, and hemodynamic; of these, nonenzymatic glycosylation of proteins and glomerular hyperfiltration appear to be most important. In the last few years, a better understanding of the natural history of type I diabetes has been gained, with particular significance attributed to the stage of the disease defined as incipient diabetic nephropathy which is characterized by microalbuminuria. However, advances in pathophysiologic notions have not always been followed by corresponding results in the prevention and therapy of diabetic nephropathy; possible reasons for this are briefly discussed. In spite of these uncertainties, the importance of achieving the best possible correction of glycemic homeostasis and of albeit initial elevations in the arterial pressure appears to be well established.


'Old' and 'new' drugs for the treatment of cancer pain.
More than 20 years ago the World Health Organization (WHO) published the booklet 'Cancer Pain Relief', including the fundamentals and clear principles, which was summarized in five simple sentences: 'by mouth', 'by the clock', 'by the ladder', 'for the individual' and 'attention to detail'. Over the years, several modifications to the analgesic ladder have been proposed, as the addition of two further steps, related to the switch of opioid and/or non-invasive route of administration, and to the use of invasive approaches, or again the skip of the second step; nevertheless the educational value and benefits related to the worldwide dissemination are of paramount importance. To date, all the guidelines are inspired by the strategy of WHO; below some of the most important international guidelines published in the last two years are compared, particularly as regards the criteria of choice of opioids for moderate/severe pain. The discussion on the role of the second step of the WHO analgesic ladder is still open. The challenge for new formulations of 'old' opioids will be to better manage cancer pain, with more tailored efficacy and possibly less side effects.


Variation in serum creatinine level is correlated to risk of type 2 diabetes.
Skeletal muscle is well established as a major target organ of insulin action, and is associated with the pathogenesis of type 2 diabetes. Therefore, we attempted to determine whether a variation in serum creatinine is related to the development of type 2 diabetes and other risk factors for diabetes. A total of 2,676 nondiabetic subjects with stable and normal renal function (estimated glomerular filtration rate >60 mL/min/1.73 m(2)) were followed up for approximately 4.5 years. New onset diabetes was defined as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated hemoglobin (HbA1c) ≥6.5%, or subjects taking antidiabetic agents. Variation of serum creatinine (ΔCre) was defined as a difference between follow-up and baseline creatinine. In subgroup analysis, body composition was examined by bioelectric impedance analysis method. A total of 106 subjects were diagnosed with new-onset diabetes during the follow-up period. Baseline serum creatinine was not different between the new-onset diabetes and no diabetes groups. Negative ΔCre (ΔCre <0) showed an association with increased risk of type 2 diabetes after adjusting for age, sex, body mass index, systolic blood pressure, FPG, HbA1c, triglyceride, high density lipoprotein cholesterol, and γ-glutamyl transpeptidase (odds ratio, 1.885; 95% confidence interval, 1.127 to 3.153). Serum creatinine level demonstrated positive correlation with muscle mass and negative correlation with percentage of body fat in body composition analysis. Serum creatinine reflected body muscle mass and the decrease of serum creatinine might be regarded as a risk factor for type 2 diabetes.


A Motion Interference-Insensitive Flexible Dry Electrode.
A novel dry electrode is developed to improve the comfortability and the capability of alleviating motion interference by combining microneedles array (MNA) with flexible substrate. Silicon MNA with sharp tips and limited height is fabricated and transferred on a flexible Polydimethylsiloxane (PDMS) substrate through bonding. Poly (3, 4-ethylenedioxythiophene) doped with poly (styrenesulfonate) (PEDOT/PSS) is coated on the surface of flexible MNA to form a conductive layer. Flexible dry electrode with 1.2 cm diameter is successfully fabricated. The mean impedance magnitudes (measured on skin) at 10 Hz are 61.2 ±31.3 kΩ·cm(2) for flexible dry electrode, while the values are 114.9 ±36.1 kΩ·cm(2) for wet electrode and 335.7 ±110.5 kΩ·cm(2) for flexible planar dry electrode, respectively. In the process of biopotential recording, the flexible dry electrode has the similar performance as that of wet electrode. It exhibits more stable recording stability than rigid dry electrode in the movement state. By integrating flexible PDMS substrate, sharp and hard MNA structure, as well as PEDOT/PSS coated surface together, a novel dry electrode is developed to meet the comfortable and antimotion interference requirement of wearable equipment. The novel flexible dry electrode provides a simple and comfortable method to record biopotential signals in daily life.


Novel Hybrid Modeling and Analysis Method for Steam Reforming Solid Oxide Fuel Cell System Multifault Degradation Fusion Assessment.
Steam reforming solid oxide fuel cell (SOFC) systems are important devices to promote carbon neutralization and clean energy conversion. It is difficult to monitor system working conditions in real time due to the possible fusion fault degradation under high temperatures and the seal environment, so it is necessary to design an effective system multifault degradation assessment strategy for solid oxide fuel cell systems. Therefore, in this paper, a novel hybrid model is developed. The hybrid model is built to look for the system fault reason based on first principles, machine learning (radial basis function neural network), and a multimodal classification algorithm. Then, stack, key balance of plant components (afterburner, heat exchanger, and reformer), thermoelectric performance, and system efficiency are studied during the progress of the system experiment. The results show that the novel hybrid model can track well the system operation trend, and solid oxide fuel cell system working dynamic performance can be obtained. Furthermore, four fault types of solid oxide fuel cell systems are analyzed with thermoelectric parameters and energy conversion efficiency based on transition and fault stages, and two cases are also successful by using the built model to decouple the multifault degradation fusion. In addition, the solid oxide fuel cell multifault degradation fusion assessment method proposed in this paper can also be used in other fuel cell systems.


Revealing the macromolecular targets of complex natural products.
Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The technique does not require three-dimensional target models and may be applied to structurally complex natural products. The algorithm dissects the natural products into fragments and infers potential pharmacological targets by comparing the fragments to synthetic reference drugs with known targets. We demonstrate that this approach results in confident predictions. In a prospective validation, we show that fragments of the potent antitumour agent archazolid A, a macrolide from the myxobacterium Archangium gephyra, contain relevant information regarding its polypharmacology. Biochemical and biophysical evaluation confirmed the predictions. The results obtained corroborate the practical applicability of the computational approach to natural product 'de-orphaning'.


Impact of Gender Difference on Anxiety in COVID-19 Patients in Quarantine Wards.
This study aimed to investigate the gender difference in anxiety in novel coronavirus pneumonia (COVID-19) patients in the quarantine ward during the outbreak. The self-rating anxiety scale (SAS) was used on the seventh day of isolation to analyze the anxiety levels of a total of 242 suspected or confirmed COVID-19 patients in the quarantine wards of two hospitals; 232 of these patients (112 males and 120 females) completed the anxiety scoring. The anxiety scores were compared between male and female patients using the t-test, and a scatter diagram was used for analysis. The SAS scores of females in quarantine wards were higher than those of males at seven days of isolation. Women with COVID-19 are more prone to anxiety than men while in isolation. It is necessary to give more attention to female patients in quarantine wards in the future, and psychological counseling may be necessary.


Translation and Test⁻Retest of the Spanish Podiatry Health Questionnaire (PHQ-S).
Background: The Podiatric Health Questionnaire (PHQ) is a health-related questionnaire consisting of six questions designed for measuring foot health status. To date, the PHQ has only been validated in the English-language version. Thus, this study aimed to perform the Spanish translation and test⁻retest procedures of the PHQ (PHQ-S). Method: The forward/backward translation and test⁻retest reliability methods were applied from English to Spanish languages. Regarding the total score for each domain, internal consistency and reliability were determined by the Cronbach α and intraclass correlation coefficient (ICC) with a confidence interval (CI) of 95%. Results: High internal consistency was shown for the six domains: (1) walking with a Cronbach α of 0.97; (2) hygiene and nail care with 0.93 and 093, respectively; (3) foot pain with 0.91; (4) worry and concern domain with 0.904; (5) quality of life with 0.87; and (6) the self-perception of how their feet are feeling measured by a visual analogic scale with 0.92. Excellent test⁻retest reliability (ICC = 0.99 (95% CI = 0.96⁻0.98)) was shown for the total score. Conclusions: The PHQ-S was shown to be a valid and reliable tool for an acceptable use in the Spanish population.


Assessing the support needs of women with early breast cancer in Australia.
The purpose of the current study was to access the degree to which the support needs of women with a newly diagnosed, early invasive, primary breast cancer and their families are being met. A random sample of 544 women diagnosed with early breast cancer was recruited to participate in a telephone survey via state and territory cancer registries. Sixteen percent of women reported not receiving enough support during their diagnosis and treatment, and only 65% of these women reported that their families received enough support. The primary sources of support for women and their families were medical practitioners (eg, surgeons, oncologists, and general practitioner) with very few women or family members utilizing mental health professionals. Given the importance of adequate support when being diagnosed and treated for breast cancer, urgent attention needs to be paid to training medical professionals in providing appropriate support and referrals for their patients.


Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a gynecologic oncology group study.
Concurrent chemoradiotherapy is the standard of care for locally advanced cervix cancer; the optimal chemotherapy regimen is not yet defined. This trial was designed to compare the outcome of protracted venous infusion (PVI) fluorouracil (FU) with standard weekly cisplatin and concurrent radiation therapy (RT). Patients with stage IIB, IIIB, and IVA cervical cancer with clinically negative aortic nodes were eligible. Pelvic RT dose was 45 Gy with a parametrial boost to involved sides of 5.4 to 9 Gy, and high- or low-dose rate intracavitary brachytherapy. Standard therapy was weekly cisplatin 40 mg/m2, and experimental therapy was PVI FU 225 mg/m2/d for 5 d/wk for six cycles during RT. The study was closed prematurely when a planned interim futility analysis indicated that PVI FU/RT had a higher treatment failure rate (35% higher) and would, most likely, not result in an improvement in progression-free survival compared with weekly cisplatin/RT. The PVI FU/RT arm continues to show a higher risk of treatment failure (relative risk [RR] unadjusted, 1.29) and a higher mortality rate (RR unadjusted, 1.37). There was no difference in pelvic treatment failure between regimens, but there was an increase in the failure rate at distant sites in the PVI FU arm. In this study, PVI FU does not show improved outcome over weekly cisplatin. Future research should explore combinations of FU with cisplatin, new radiosensitizers, and active drugs combined with RT to reduce the high rate of pelvic and distant treatment failure still seen in advanced cervix cancer.


[Morphologic variants of genital ulcer caused by Haemophilus ducreyi].
The typical clinical picture, common variants and frequent complications of chancroid are presented in cases proven by culture. In general, the conventional view of the clinical spectrum of chancroid is substantiated. Certain types such as "chancre mou volant," however, could not be found in the present material. Their existence or association with Haemophilus ducreyi remains speculative.


Rupture of donor ascending aorta following heart transplantation.
Among 81 patients who underwent orthotopic heart transplantation between July 1986 and December 1990, we found rupture of the donor ascending aorta in three patients, all with severe ventricular dysfunction secondary to aortic valvular disease. The mechanism for this may be compliance mismatch between the recipient ascending aorta and the donor ascending aorta. This situation is a unique complication in heart transplantation for the recipients who have severe athero-sclerotic changes in the systemic aortic wall, especially for those with valvular diseases caused by calcification.


Importance of prognostic factors in cancer clinical trials.
The importance of prognostic factors in the design, analysis, and reporting of clinical trials is discussed. For many kinds of cancer, the variability in prognosis among patients is greater than the size of treatment differences usually seen. Consequently, failure to understand and adequately account for patient heterogeneity easily leads to unreliable claims and inefficient trials. Identified prognostic factors are generally of sufficient importance to demand attention in design and analysis, but rarely are sufficiently explanatory to render randomization unnecessary. Improvement in knowledge of prognostic factors is important for sharpening the focus and for improving the reliability, efficiency, and interpretability of clinical trials. Problems in the conduct of prognostic factor studies are also discussed, and the calculation of the proportion of variability explained by logistic regression models is illustrated for two examples.


Chromosome copy number variation and control in the ciliate Chilodonella uncinata.
Copy number variations are widespread in eukaryotes. The unusual genome architecture of ciliates, in particular, with its process of amitosis in macronuclear division, provides a valuable model in which to study copy number variation. The current model of amitosis envisions stochastic distribution of macronuclear chromosomes during asexual reproduction. This suggests that amitosis is likely to result in high levels of copy number variation in ciliates, as dividing daughter cells can have variable copy numbers of chromosomes if chromosomal distribution during amitosis is a stochastic process. We examined chromosomal distribution during amitosis in Chilodonella uncinata, a ciliate with gene-size macronuclear chromosomes. We quantified 4 chromosomes in evolving populations of C. uncinata and modeled the amitotic distribution process. We found that macronuclear chromosomes differ in copy number from one another but that copy number does not change as expected under a stochastic process. The chromosome carrying SSU increased in copy number, which is consistent with selection to increase abundance; however, two other studied chromosomes displayed much lower than expected among-line variance. Our models suggest that balancing selection is sufficient to explain the observed maintenance of chromosome copy during asexual reproduction.


Discovery, mechanism and metabolism studies of 2,3-difluorophenyl-linker-containing PARP1 inhibitors with enhanced in vivo efficacy for cancer therapy.
Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially breast and ovarian cancers, and tumor cell lines deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this study, with the help of molecular docking, we identified a novel series of 2,3-difluorophenyl-linker analogues (15-54) derived from olaparib (1) as PARP1 inhibitors. Lead optimization led to the identification of 47, which showed high selectivity and high potency against PARP1 enzyme (IC50 = 1.3 nM), V-C8 cells (IC50 = 0.003 nM), Capan-1 cells (IC50 = 7.1 nM) and MDA-MB-436 cells (IC50 = 0.2 nM). Compound 47 had more potent PARP1-DNA trapping and double-strand breaks (DSBs)-induction activities than 1 and induced G2/M arrest and caspase-dependent apoptosis. Compound 47 (50 mg/kg, 94.2%) had a more beneficial effect on tumor growth inhibition than 1 (100 mg/kg, 65.0%) in a BRCA1-mutated xenograft model and significantly inhibited tumor growth (40 mg/kg, 48.1%) in a BRCA2-mutated xenograft model, with no negative influence on the body weight of the mice. Collectively, these data demonstrated that 47 might be an excellent drug candidate for the treatment of cancer, especially for BRCA-deficient tumors.


A mathematical model for short-term vs. long-term survival in patients with glioma.
Gliomas, the most common primary brain tumors in adults, constitute clinically, histologically, and molecularly a most heterogeneous type of cancer. Owing to this, accurate clinical prognosis for short-term vs. long-term survival for patients with grade II or III glioma is currently nonexistent. A rigorous, multi-method bioinformatic approach was used to identify the top most differentially expressed genes as captured by mRNA sequencing of tumor tissue. Mathematical modeling was employed to develop the model, and three different and independent methods of validation were used to assess its performance. I present here a mathematical model that can identify with a high accuracy (sensitivity=92.9%, specificity=96.0%) those patients with glioma (grade II or III) who will experience short-term survival (≤ 1 year), as well as those with long-term survival (≥ 3 years), at the time of diagnosis and prior to surgery and adjuvant chemotherapy. The 5 gene input variables to the model are: FAM120AOS, PDLIM4, OCIAD2, PCDH15, and MXI1. MXI1, a transcriptional repressor, represents the top biomarker of survival and the most promising target for the development of a pharmacological treatment.


The achilles heel of the trojan horse model of HIV-1 trans-infection.
To ensure their survival, microbial pathogens have evolved diverse strategies to subvert host immune defenses. The human retrovirus HIV-1 has been proposed to hijack the natural endocytic function of dendritic cells (DCs) to infect interacting CD4 T cells in a process termed trans-infection. Although DCs can be directly infected by certain strains of HIV-1, productive infection of DCs is not required during trans-infection; instead, DCs capture and internalize infectious HIV-1 virions in vesicles for later transmission to CD4 T cells via vesicular exocytosis across the infectious synapse. This model of sequential endocytosis and exocytosis of intact HIV-1 virions has been dubbed the "Trojan horse" model of HIV-1 trans-infection. While this model gained rapid favor as a strong example of how a pathogen exploits the natural properties of its cellular host, our recent studies challenge this model by showing that the vast majority of virions transmitted in trans originate from the plasma membrane rather than from intracellular vesicles. This review traces the experimental lines of evidence that have contributed to what we view as the "rise and decline" of the Trojan horse model of HIV-1 trans-infection.


Early hemoglobin response and alternative metrics of efficacy with erythropoietic agents for chemotherapy-related anemia.
To examine associations between early hemoglobin response and alternative measures of efficacy following treatment with an erythropoietic agent for chemotherapy-related anemia. Preliminary data from an ongoing randomized, multicenter, 16-week, open-label clinical trial of epoetin alfa versus darbepoetin alfa were used to dichotomize patients based on attainment of early hemoglobin response (> or = 1 g/dL increase in hemoglobin level within 4 weeks of treatment initiation). Measures of efficacy were compared between patients with early hemoglobin response and those without. Sensitivity analyses were then performed to evaluate the impact of various methods for handling censored data and hemoglobin values following blood transfusion. Efficacy measures included: the proportion of patients with a > or = 1 g/dL increase in hemoglobin by 4 weeks or a > or = 2 g/dL increase by 8 weeks; mean hemoglobin levels at 4, 8, 12, and 16 weeks; area under the curve for change in hemoglobin level; proportion of patients who required a blood transfusion after 4 weeks; proportion of follow-up days on which patients had hemoglobin levels within the therapeutic range of 11 g/dL to 13 g/dL; and proportion of patients who never had a hemoglobin level within this range. A total of 274 patients were included (66.1% female, mean age 62.4), of whom 48.9% had an early hemoglobin response and 51.1% did not. Mean duration of follow-up was 10.1 +/- 5.05 weeks. All metrics indicated superior longer-term response among patients with early hemoglobin response compared to patients without early response. The findings were robust across sensitivity analyses. Although the analysis establishes a significant relationship between early hemoglobin response and alternative efficacy metrics, causality cannot be inferred. Early hemoglobin response is significantly associated with various metrics of clinical response to erythropoietic agents and is an appropriate measure for evaluating treatment effects.


Pharmacological Treatments in Heart Failure With Mildly Reduced and Preserved Ejection Fraction: Systematic Review and Network Meta-Analysis.
Medical treatment for heart failure (HF) with preserved ejection (HFpEF) and with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with reduced ejection fraction, despite recent trials with an angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). We aimed to estimate the aggregate therapeutic benefit of drugs for HFmrEF and HFpEF. We performed a systematic review of MEDLINE, CENTRAL, and Web of Science for randomized trials including patients with HF and left ventricular ejection fraction (LVEF) >40%, treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (analyzed together as renin-angiotensin system inhibitors [RASi]), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, and SGLT2i. An additive component network meta-analysis was performed. The primary outcome was a composite of cardiovascular (CV) death and first hospitalization for heart failure (HHF); secondary outcomes were CV death, total HHF, and all-cause mortality. We identified 13 studies with a total of 29,875 patients and a mean LVEF of 56.3% ± 8.7%. ARNI, MRA, and SGLT2i separately, but not RASi, BB, or digoxin, reduced the primary composite outcome compared with placebo. The combination of ARNI, BB, MRA, and SGLT2i was the most effective (HR: 0.47 [95% CI: 0.31-0.70]); this was largely explained by the triple combination of ARNI, MRA, and SGLT2i (HR: 0.56 [95% CI 0.43-0.71]). Results were similar for CV death (HR: 0.63 [95% CI 0.43-0.91] for ARNI, MRA, and SGLT2i) or total HHF (HR: 0.49 [95% CI 0.33-0.71] for ARNI, MRA, and SGLT2i) alone. In a subgroup analysis, only SGLT2i had a consistent benefit among all LVEF subgroups, whereas the triple combination had the greatest benefit in HFmrEF, robust benefit in patients with LVEF 50% to 59%, and a statistically marginal benefit in patients with LVEF ≥60%. In patients with HF and LVEF>40%, the quadruple combination of ARNI, BB, MRA, and SGLT2i provides the largest reduction in the risk of CV death and HHF; driven by the robust effect of the triple combination of ARNI, MRA, and SGLT2i. The benefit was more pronounced in HFmrEF patients.


In Vitro and In Vivo Antimicrobial Activity of an Oxidative Stress-Mediated Bicyclic Menaquinone Biosynthesis Inhibitor against MRSA.
Menaquinone (MK) is an essential component in the oxidative phosphorylation pathway of Gram-positive bacteria. Drugs targeting enzymes involved in MK biosynthesis can prevent electron transfer, which leads to ATP starvation and thereby death of microorganisms. Previously, we reported a series of MenA inhibitors and demonstrated their antimicrobial activity against Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA) and mycobacteria. These inhibitors were developed by mimicking demethylmenaquinone, a product of MenA enzymatic reaction in MK biosynthesis. In this study, compound NM4, MK biosynthesis inhibitor, inhibited the formation of MRSA biofilm and it was screened against 1952 transposon mutants to elucidate mechanisms of action; however, no resistant mutants were found. Also, compound NM4 induced the production of reactive oxygen species (ROS) by blocking electron transfer in the oxidative phosphorylation pathway as observed by MRSA growth recovery using various ROS scavengers. An oxygen consumption assay also showed that NM4 blocks the oxygen consumption by MRSA, but the addition of menaquinone (MK) restores growth of MRSA. The NM4-treated MRSA induced the expression of catalase by more than 25%, as quantified by the native gel. A pulmonary murine model exhibited that NM4 significantly reduced bacterial lung load in mice without toxicity. An NM4-resistant USA300 strain was developed to attempt to identify the targets participating in the mechanism of resistance. Our results support that respiration and oxidative phosphorylation are potential targets for developing antimicrobial agents against MRSA. Altogether, our findings suggest the potential use of MK biosynthesis inhibitors as an effective antimicrobial agent against MRSA.


Decoronation: An Alternative Treatment for Replacement Root Resorption.
Ankylosis and disrupted or altered root development are frequent complications associated with intrusive luxation and tooth avulsion lesions. Various forms of treatment have been described according to the severity of the trauma and root development. The literature shows that decoronation is an ideal treatment in cases where replacement resorption occurs. Two clinical cases are presented: involving intrusive luxation [15-year-old female patient with an affected maxillary left lateral incisor (2.2)] and a replanted avulsed tooth [8-year-old male patient with avulsion of the right maxillary central incisor (1.1)]; both cases presented advanced root resorption so that decoronation with a prosthetic tooth replacement was decided as the final treatment option. In the short-term follow-up, patients were asymptomatic and had no functional problems. Radiographs showed that crestal bone height had been preserved. Preserving the decoronated root in the alveolar process not only helps to maintain bone volume but also enables vertical bone growth and facilitates the future insertion of an implant.


Efficacy of clarithromycin in pityriasis rosea.
To determine the efficacy of clarithromycin in the treatment of Pityriasis Rosea (PR). Double blind randomized controlled trial. Dermatology OPD, Military Hospital, Rawalpindi, from July 2008 to July 2009. Patients aged above 10 years, diagnosed with PR, were randomly assigned to two groups of 30 each to receive either clarithromycin or similar-looking placebo for one week. Neither the patient nor the treating physician knew to which group the patient belonged. Patients were assessed at 1, 2, 4 and 6 weeks after presentation and compared for complete, partial or no response. Among the 60 patients, no significant difference was found between the two groups at 2 weeks after presentation (p = 0.598). In the placebo group, complete response was seen in 20 (66.7%), partial response in 3 (10.0%) while no response was seen in 7 (23.3%). In clarithromycin group, there was complete response in 23 (76.7%), partial response in 3 (10.0%) and no response in 4 (13.3%) patients. Clarithromycin is not effective in treatment of pityriasis rosea.


The effect of consumption temperature on the homeostatic and hedonic responses to glucose ingestion in the hypothalamus and the reward system.
Excessive consumption of sugar-sweetened beverages (SSBs) has been associated with obesity and related diseases. SSBs are often consumed cold, and both the energy content and temperature might influence the consumption behavior for SSBs. The main aim of this study was to elucidate whether consumption temperature and energy (i.e., glucose) content modulate homeostatic (hypothalamus) and reward [ventral tegmental area (VTA)] responses. Sixteen healthy men participated in our study [aged 18-25 y; body mass index (kg/m2): 20-23]. High-resolution functional magnetic resonance imaging data were collected after ingestion of 4 different study stimuli: plain tap water at room temperature (22°C), plain tap water at 0°C, a glucose-containing beverage (75 g glucose dissolved in 300 mL water) at 22°C, and a similar glucose drink at 0°C. Blood oxygen level-dependent (BOLD) changes from baseline (7 min preingestion) were analyzed over time in the hypothalamus and VTA for individual stimulus effects and for effects between stimuli. In the hypothalamus, water at 22°C led to a significantly increased BOLD response; all other stimuli resulted in a direct, significant decrease in BOLD response compared with baseline. In the VTA, a significantly decreased BOLD response compared with baseline was found after the ingestion of stimuli containing glucose at 0°C and 22°C. These responses were not significantly modulated by consumption temperature. The consumption of plain water did not have a significant VTA BOLD effect. Our data show that glucose at 22°C, glucose at 0°C, and water at 0°C lowered hypothalamic activity, which is associated with increased satiation. On the contrary, the consumption of water at room temperature increased activity. All stimuli led to a similar VTA response, which suggests that all drinks elicited a similar hedonic response. Our results indicate that, in addition to glucose, the low temperature at which SSBs are often consumed also leads to a response from the hypothalamus and might strengthen the response of the VTA. This trial was registered at www.clinicaltrials.gov as NCT03181217.


Characterization of Critical Functions of Long Non-Coding RNAs and mRNAs in Rhabdomyosarcoma Cells and Mouse Skeletal Muscle Infected by Enterovirus 71 Using RNA-Seq.
Enterovirus 71 (EV71) is the main pathogen of severe hand-foot-mouth disease (HFMD). Long non-coding RNAs (lncRNAs) are recognized as pivotal factors during the pathogenesis of viral infection. However, the critical functions of lncRNAs in EV71⁻host interactions have not been characterized. Here, for the first time, we performed global transcriptome analysis of lncRNA and mRNA expression profiles in EV71-infected human rhabdomyosarcoma (RD) cells and skeletal muscle of mice using second-generation sequencing. In our study, a total of 3801 novel lncRNAs were identified. In addition, 23 lncRNAs and 372 mRNAs exhibited remarkable differences in expression levels between infected and uninfected RD cells, while 104 lncRNAs and 2647 mRNAs were differentially expressed in infected skeletal muscle from neonatal mice. Comprehensive bioinformatics analysis included target gene prediction, lncRNA‑mRNA co-expression network construction, as well as gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis mainly focused on differentially-expressed genes (DEGs). Our results suggest that lncRNAs may participate in EV71 infection-induced pathogenesis through regulating immune responses, protein binding, cellular component biogenesis and metabolism. The present study provides novel insights into the functions of lncRNAs and the possible pathogenic mechanism following EV71 infection.


Simultaneous laparoscopic resection of rectal cancer and liver metastasis.
Simultaneous resection of colorectal tumor and liver metastasis has been advocated because of the benefits of avoiding a second operation, reduced morbidity, shorter treatment time, and similar outcomes. We report a case of simultaneous laparoscopic resection. The operative time was 350 minutes and the estimated blood loss was 500 mL. The patient required parenteral analgesia for less than 48 hours. Flatus was passed on postoperative day 3, and a solid diet was resumed on postoperative day 5. He was fully mobile on postoperative day 4 and was discharged 3 days later. With the advance of laparoscopic technology and technique, simultaneous resection becomes an attractive option.


Streamlined design of a self-inactivating feline immunodeficiency virus vector for transducing ex vivo dendritic cells and T lymphocytes.
Safe and efficient vector systems for delivering antigens or immunomodulatory molecules to dendritic cells (DCs), T lymphocytes or both are considered effective means of eliciting adaptive immune responses and modulating their type, extent, and duration. As a possible tool toward this end, we have developed a self-inactivating vector derived from feline immunodeficiency virus (FIV) showing performance characteristics similar to human immunodeficiency virus-derived vectors but devoid of the safety concerns these vectors have raised. The pseudotyped FIV particles were generated with a three-plasmid system consisting of: the packaging construct, providing Gag, Pol and the accessory proteins; the vector(s), basically containing FIV packaging signal (psi), Rev responsive element, R-U5 region at both ends, and the green fluorescent protein as reporter gene; and the Env plasmid, encoding the G protein of vesicular stomatitis virus (VSV-G) or the chimeric RD114 protein. Both packaging and vector constructs were derived from p34TF10, a replication competent molecular clone of FIV. The pseudotyped particles were produced by transient transfection in the Crandell feline fibroblast kidney (CrFK) or the human epithelial (293T) cell line. To broaden its species tropism, the final vector construct was achieved through a series of intermediate constructs bearing a longer psi, the FIV central polypurin tract sequence (cPPT), or the woodchuck hepatitis post-regulatory element (WPRE). These constructs were compared for efficiency and duration of transduction in CrFK or 293T cells and in the murine fibroblast cell line NIH-3T3. Whereas psi elongation and cPPT addition did not bring any obvious benefit, insertion of WPRE downstream GFP greatly improved vector performances. To maximize the efficiency of transduction for ex-vivo murine DCs and T-lymphocytes, this construct was tested with VSV-G or RD114 and using different transduction protocols. The results indicated that the FIV construct derived herein stably transduced both cell types, provided that appropriate vector makeup and transduction protocol were used. Further, transduced DCs underwent changes suggestive of an induced maturation. In contrast to previously described FIV vectors that were poorly efficient in delivering genetic material to DCs and T lymphocytes, the vector developed herein has potential for use in experimental immunization strategies.