Editorial Commentary: Large-Diameter Quadrupled Hamstring Autografts Are an Acceptable Option for National Collegiate Athletic Association Division I College Football Players: We Must Challenge Our Comfort Zone to Be Successful in the End Zone.
The majority of surgeons caring for elite American football teams choose bone-patellar tendon-bone (BTB) autograft for anterior cruciate ligament reconstruction. As we strive to continue to improve currently favorable outcomes, we need to consider all options regarding graft choice, surgical technique, and postoperative rehabilitation. Advantages of BTB include an excellent track record, potential for faster incorporation with bone-to-bone healing. Disadvantages include risk of patellar fracture/tendon rupture and anterior knee pain. The pros of quadrupled hamstring (QH) graft include stronger graft (higher ultimate load to failure) and less anterior knee pain and stiffness, and the cons include loss of flexion/hamstring strength and slower healing in the tunnels. Several studies have shown that smaller grafts have higher failure rates, and recent research shows that QH grafts >9 mm had decreased risk of revision compared to BTB. We can now quadruple the semitendinosus tendon to provide elite athletes with even more robust grafts. Large-diameter QH autografts are an acceptable option for National Collegiate Athletic Association Division I college football players.


Oligometastatic Prostate Cancer: A Comparison between Multimodality Treatment vs. Androgen Deprivation Therapy Alone.
Background: We compared multimodality treatment (MMT, defined as robot-assisted radical prostatectomy (RARP) with androgen deprivation therapy (ADT), with or without adjuvant radiotherapy (RT)) vs. ADT alone in oligometastatic prostate cancer (OPC) patients. Methods: From 2010 to 2018, we identified 74 patients affected by cM1a-b OPC (≤5 metastases). Kaplan−Meier (KM) plots depicted cancer-specific mortality (CSM), disease progression, metastatic castration-resistant PC (mCRPC), and time to second-line systemic therapy rates. Multivariable Cox regression models (MCRMs) focused on disease progression and mCRPC. Results: Forty (54.0%) MMT and thirty-four (46.0%) ADT patients were identified. On KM plots, higher CSM (5.9 vs. 37.1%; p = 0.02), mCRPC (24.0 vs. 62.5%; p < 0.01), and second-line systemic therapy (33.3 vs. 62.5%; p < 0.01) rates were recorded in the ADT group. No statistically significant difference was recorded for disease progression. ForMCRMs adjusted for the metastatic site and PSA, a higher mCRPC rate was recorded in the ADT group. No statistically significant difference was recorded for disease progression. Treatment-related adverse events occurred in 5 (12.5%) MMT vs. 15 (44.1%) ADT patients (p < 0.01). Conclusions: MMT was associated with lower CSM, mCRPC, and second-line therapy rates. A lower rate of treatment-related adverse events was recorded for the MMT group.


Embryo survival in heifers after transfer of an egg to the uterine horn contralateral to the corpus luteum and the effect of treatments with progesterone or hCG on pregnancy rates.
Day 7 eggs (oestrus = Day 0) were surgically transferred singly to the uterine horn contralateral to the CL and heifers were either slaughtered on Day 24-26 (Group 1) or palpated per rectum on Day 42 (Group 2) to determine the presence of a developing conceptus and a maintained corpus luteum. There was a fall in pregnancy rate of the control heifers in Groups 1a (6/10) and 2a (2/10) (P = 0.085). Pregnancy rate was unaffected by progesterone treatments from Day 13 to the day before slaughter in Group 1b (8/10), or to Day 23 in Group 2b (2/10). Two of the conceptuses recovered in Group 1b were developing in the presence of regressed corpora lutea. There was, however, an increase in pregnancy rate in Group 2d (6/10) compared with Group 2a (2/10) when heifers were treated with hCG from Days 13 to 35 (P = 0.085). The results indicated that embryonic death is occurring after Day 24 and suggest that a change in the nature of the embryonic signal may be occurring at this time.


Differential scattering of circularly polarized light as a unique probe of polynucleosome superstructures. A simulation by multiple scattering of dipoles.
A theoretical approach to modeling Circular Intensity Differential Scattering (CIDS) of native chromatin as multiple scattering of dipoles is discussed without the Born approximation. The model can explain the experimental data in the literature. It is shown that CIDS contains more structural information than does total light scattering and to a good approximation is independent of the length of the scattering molecules. Finally, CIDS in conjunction with traditional light scattering measurements should aid in discriminating between various alternative models of higher order chromatin structure now being proposed. Generalization of this theoretical study to other complex biomolecular structures, is also briefly discussed.


Complement in Neurologic Disease.
Classic innate immune signaling pathways provide most of the immune response in the brain. This response activates many of the canonical signaling mechanisms identified in peripheral immune cells, despite their relative absence in this immune-privileged tissue. Studies over the past decade have strongly linked complement protein production and activation to age-related functional changes and neurodegeneration. The reactivation of the complement signaling pathway in aging and disease has opened new avenues for understanding brain aging and neurological disease pathogenesis and has implicated cell types such as astrocytes, microglia, endothelial cells, oligodendrocytes, neurons, and even peripheral immune cells in these processes. In this review, we aim to unravel the past decade of research related to complement activation and its numerous consequences in aging and neurological disease.


Some psychoanalytic reflections on the concept of dignity.
After reviewing the pertinent philosophical and psychoanalytic writings on the concept of dignity, this paper proposes three categories of dignity. Conceptualized as phenomenological clusters, heuristic viewpoints, and levels of abstraction, these include (i) metaphysical dignity which extends the concept of dignity beyond the human species to all that exists in this world, (ii) existential dignity which applies to human beings alone and rests upon their inherent capacity for moral transcendence, and (iii) characterological dignity which applies more to some human beings than others since they possess a certain set of personality traits that are developmentally derived. The paper discusses the pros and cons of each category and acknowledges the limitations of such classification. It also discusses the multiple ways in which these concepts impact upon clinical work and concludes with some remarks on the relationship of dignity to choice, narcissism, and suicide.


Oxidovanadium(V) complexes as promising anticancer photosensitizers.
Photodynamic therapy (PDT) is an alternative treatment widely used against cancer. PDT requires molecular systems, known as photosensitizers (PS), which not only exhibit strong absorption at a particular wavelength range, but also need to be selectively accumulated inside cancer cells. PS are activated by specific wavelengths that cause tumor cell death by mechanisms related with oxidative stress. In this paper, three oxidovanadium(V) complexes linked to a Schiff base, which exhibit anticancer activity by displaying desirable accumulation inside malignant cells, are studied using Density Functional Theory (DFT) and Time Dependent-DFT (TD-DFT) methodologies to characterize their structural and photophysical properties as possible PS. The maximum absorption of these complexes in aqueous solution was predicted to be approximately 460 nm presenting a ligand-to-metal charge transfer. Additionally, we describe the photodynamic type reaction that these complexes can undergo when considered as PS candidates. Our results suggest that the system, containing triethylammonium as substituent, is the most suitable complex to act both as PS and as a possible therapeutic candidate in PDT.


Central Nervous System Metastases.
The proportion of patients developing central nervous system (CNS) metastasis is increasing. Most are identified once symptomatic. Surgical resection is indicated for solitary or symptomatic brain metastases, separation surgery for compressive radioresistant spinal metastases, and instrumentation for unstable spinal lesions. Surgical biopsies are performed when histological diagnoses are required. Stereotactic radiosurgery is an option for limited small brain metastases and radioresistant spinal metastases. Whole-brain radiotherapy is reserved for extensive brain metastases and leptomeningeal disease with approaches to reduce cognitive side effects. Radiosensitive and inoperable spinal metastases typically receive external beam radiotherapy. Systemic therapy is increasingly being utilized for CNS metastases.


Digital image colorimetry detection of carbaryl in food samples based on liquid phase microextraction coupled with a microfluidic thread-based analytical device.
This research used a digital image colorimetry (DIC) method to detect carbaryl in food samples using effervescence-assisted liquid phase microextraction based on solidification of switchable hydrophilicity solvent combined with a microfluidic thread-based analytical device (EA-LPME-SSHS-μTAD). 1-naphthol, the hydrolysate of carbaryl, was extracted into octanoic acid by the adjustment of pH values of the sample solution and separated through solidification in an ice bath. Then 1-naphthol contained in the extracted solution was coupled with 4-methoxybenzenediazonlum tetrafluoroborate (MBDF) fixed on the μTAD to produce tangerine compounds. The inherent colour variation was captured by a smartphone and processed to calculate the intensity (I). Under the optimal conditions, the limit of quantification was within 0.020-0.027 mg kg-1. The recovery was varied in the range from 92.3% to 105.9% with a relative standard deviation (RSD) below 5%. The developed method provides an alternative strategy to extract and detect pesticides for food samples.


What the public in England know about antibiotic use and resistance in 2020: a face-to-face questionnaire survey.
To describe public attitudes and knowledge around antibiotic activity, resistance and use. Face-to-face household 18 question survey using computer-assisted data collection undertaken by Ipsos Market and Opinion Research International. Randomly selected households across England, January-February 2020. 2022 adults (aged 15+,) including 521 black, Asian and minority ethnic (BAME) participants, and 406 aged 15-25 years olds. Responses to questions about antibiotic activity, resistance and expectations for antibiotics and trust in healthcare professionals. Analyses were weighted to obtain estimates representative of the population with multivariable analysis undertaken for questions with five or more significant univariate variables. 84% stated they would be pleased if their general practitioner (GP) said they did not need antibiotics. Trust in GPs to make antibiotic decisions remains high (89%) and has increased for nurses (76%) and pharmacists (71%). Only 21% would challenge an antibiotic decision; this was significantly greater in BAME participants (OR 2.5; 95% CI 1.89 to 3.35). 70% reported receiving advice when prescribed antibiotics. Belief in benefits of antibiotics for ear infections was very high (68%). Similar to 2017, 81% agreed that antibiotics work for bacterial, 28% cold and influenza viruses. 84% agreed antibiotic resistant bacteria (ARB) are increasing, only 50% agreed healthy people can carry ARB and 39% agreed there was nothing they personally could do about ARB. Social grade DE and BAME participants, and those with less education had significantly less understanding about antibiotics and resistance. As trust in healthcare practitioners is high, we need to continue antibiotic education and other interventions at GP surgeries and community pharmacies but highlight that most ear infections are not benefitted by antibiotics. Targeted interventions are needed for socioeconomic DE, BAME groups and previous antibiotic users. We need to explore if increasing perceived personal responsibility for preventing ARB reduces antibiotic use.


Cell cycle arrest and induction of apoptosis by cajanin stilbene acid from Cajanus cajan in breast cancer cells.
The low abundant cajanin stilbene acid (CSA) from Pigeon Pea (Cajanus cajan) has been shown to kill estrogen receptor α positive cancer cells in vitro and in vivo. Downstream effects such as cell cycle and apoptosis-related mechanisms have not been analyzed yet. We analyzed the activity of CSA by means of flow cytometry (cell cycle distribution, mitochondrial membrane potential, MMP), confocal laser scanning microscopy (MMP), DNA fragmentation assay (apoptosis), Western blotting (Bax and Bcl-2 expression, caspase-3 activation) as well as mRNA microarray hybridization and Ingenuity pathway analysis. CSA induced G2/M arrest and apoptosis in a concentration-dependent manner from 8.88 to 14.79 µM. The MMP broke down, Bax was upregulated, Bcl-2 downregulated and caspase-3 activated. Microarray profiling revealed that CSA affected BRCA-related DNA damage response and cell cycle-regulated chromosomal replication pathways. CSA inhibited breast cancer cells by DNA damage and cell cycle-related signaling pathways leading to cell cycle arrest and apoptosis.


Peritoneal dialysis in small laboratory animals.
Healthy rats and guinea-pigs were treated with a simple method of continuous peritoneal dialysis for 12, 24 and 48 h. Increasing with time, both animal species developed severe hypoproteinemia and hemoconcentration due to protein loss into the dialyzate fluid. These changes were associated with a high mortality rate, when Sterofundin was used for dialysis. Therefore, protein loss should be substituted and the type of dialyzate must be considered in experimental long-term dialysis using these small laboratory animals.


Lymphangioma circumscriptum of the scrotum: Case report.
Lymphangioma circumscriptum (LC) is the most common form of cutaneous lymphangioma. However, scrotal LC is rare. We report a case of a 37-year-old patient with a complaint of a slow growing painless scrotal grouped lesions present for the past ten years diagnosed as LC. The disorder is clinically identified by translucent or hazy vesicles of different sizes which are grouped like frog spawn or, less commonly, as diffuse swelling to a particular area. The definitive diagnosis is usually made by biopsy. LC tends to be asymptomatic. However, it can be complicated. The treatment involves medical and surgical procedures. Scrotal LC is rare and tends to mimic certain infectious diseases. The clinicians should be aware of LC in adult males without a prior disease to avoid missing the diagnosis and to prevent inappropriate treatment.


Synthesis and pharmacological screening of some N-carboxymethylbarbituric acid derivatives. I.
Reaction of haloacetate with barbital and methylphenobarbital in polar aprotic solvents in the presence of anhydrous K2CO3 gave N-carboalkoxymethyl derivatives in good yields. Acidic hydrolysis of the latter compounds affords N-carboxymethyl derivatives of barbital 8 or methylphenobarbital 7. From acid 7 and 8 via acid chlorides, amides 11--20 were prepared. These amides lack anticonvulsant activity and show only slight sedative and analgesic action.


Comparison of ivermectin and thiabendazole for treatment of naturally occurring nematode infections of goats in Kenya.
The anthelmintic activity of thiabendazole (TBZ) at 88 mg kg-1 and ivermectin at 0.2 mg kg-1 was examined in goats with naturally-acquired nematode infections. In one experiment, a herd of 450 does was treated with TBZ or ivermectin at 4-week intervals for 9 months and efficacy was measured by reduction in faecal egg counts after each treatment. In a second experiment, 100 kids were treated with ivermectin and effectiveness measured at 2 and 4 weeks after treatment by comparison of their egg counts with those of nontreated controls. In a third experiment, efficacy of treatment with TBZ and ivermectin was determined by recovery of parasites at necropsy in a controlled test with 15 kids. The results indicated that TBZ generally did not reduce egg counts and only removed 19% of Haemonchus contortus in the controlled test. The efficacy of ivermectin approached 100% for reduction in egg counts and elimination of H. contortus. Species of Ostertagia, Trichostrongylus, Nematodirus and Oesophagostomum also were present in some subjects, but not in sufficient numbers to evaluate effectiveness of treatment.


Measuring MIF in Biological Fluids.
MIF is a key regulator of host immune responses and increased levels secreted from cells, or found circulating systemically, have been implicated in the pathogenesis of many inflammatory and autoimmune disorders. Here, we describe methods for detecting and quantifying extracellular concentrations of MIF in both human- and murine-derived biological samples.


[Long-term results of posterior chamber phakic intraocular lens implantation for correction of high ametropia].
To assess efficacy, stability and safety of posterior chamber phakic intraocular lens implantation with STAAR Visian ICL for correction of high ametropia, with a mean follow-up of 5 years (3.5-10 years). Ninety eyes of 53 highly ametropic patients (45 myopia, ten hyperopia and 35 with mixed astigmatism) were included in a retrospective single-surgeon study, using primarily the V4 ICL model (87 eyes). We studied pre- and postoperative refractive efficacy, endothelial cell density, crystalline lens opacification and intraocular clearances within the various compartments of the eye. Mean uncorrected visual acuity was 0.77 at the 12th postoperative month; 17 of 90 eyes required adjunctive photoablation for residual astigmatism. Forty-eight percent of eyes gained at least one line of best corrected visual acuity. After implantation, the decrease in endothelial cell density remained stable at 0.69%/year, and 91% of eyes showed no opacification of the crystalline lens. Mean endothelium-ICL and ICL-crystalline lens distances were 2.41 mm and 0.52 mm respectively. Overall patient satisfaction achieved was 96% at 36 months postoperatively. These results demonstrate efficacy, stability and safety of the ICL V4 phakic IOL for the correction of high ametropia. Long-term follow-up did not show a significant increase in cataract formation in implanted eyes.


Synthesis of a magnosalin derivative, 4-(3,4,5-trimethoxyphenyl)-6-(2,4,5-trimethoxyphenyl)-2-diethylaminopyrimidine, and the anti-angiogenic and anti-rheumatic effect on mice by oral administration.
We describe here the synthesis and the anti-angiogenic and anti-rheumatic activities of 4-(3,4,5-trimethoxyphenyl)-6-(2,4,5-trimethoxyphenyl)-2-diethylaminopyrimidine (TAS-202), a derivative of magnosalin, which is a natural product isolated from Flos magnoliae. TAS-202 inhibited the proliferation of vascular endothelial cells more potently than magnosalin, and when given orally it inhibited basic fibroblast growth factor (bFGF)-induced angiogenesis and collagen-induced arthritis in mice. This magnosalin derivative with anti-angiogenic effects is a candidate for the treatment of rheumatoid arthritis.


An iterative approach to the analysis of EM autoradiographs. II. Estimates of sample sizes and confidence limits.
The errors inherent in EM autoradiography are discussed and certain of them deemed to be of particular practical significance in the quantitative assessment of preparations. A method is described for estimating the standard errors attributable to each of several sources of variation and thence for obtaining the overall standard error value to be attached to relative activity estimates obtained in the method of Downs & Williams (1978). In an appendix, a fully worked example is given illustrating clearly the strategy of the method and the magnitudes of error estimates that are to be attached to the final specific activity values.


Structure and mutation of a gene encoding a Mr 33,000 phycocyanin-associated linker polypeptide.
The gene encoding a phycocyanin-associated linker polypeptide of Mr 33,000 from the cyanobacterium Synechococcus sp. PCC 7002 was found to be located adjacent and 3' to the genes encoding the alpha and beta subunits of phycocyanin. The identity of this gene, designated cpcC, was proven by matching the amino-terminal sequence of the authentic polypeptide with that predicted by the nucleotide sequence. A cpcC mutant strain of this cyanobacterium was constructed. The effect of the mutation was to prevent assembly of half the total phycocyanin into phycobilisomes. By electron microscopy, phycobilisomes from this mutant were shown to contain rod substructures composed of a single disc of hexameric phycocyanin, as opposed to two discs in the wild type. It was concluded that the Mr 33,000 linker polypeptide is required for attachment of the core-distal phycocyanin hexamer to the core-proximal one. Using absorption spectra of the wild type, CpcC-, and phycocyanin-less phycobilisomes, the in situ absorbances expected for specific phycocyanin-linker complexes were calculated. These data confirm earlier findings on isolated complexes regarding the influence of linkers on the spectroscopic properties of phycocyanin.


Tivozanib: First Global Approval.
Tivozanib (Fotivda®) is an oral, potent and highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor that has been approved in the EU, Iceland and Norway for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mammalian target of rapamycin (mTOR) pathway inhibitor-naive following disease progression after one prior treatment with cytokine therapy for advanced RCC. Tivozanib is at various stages of development in other countries for advanced RCC and advanced solid tumours. This article summarizes the milestones in the development of tivozanib leading to this first global approval in Europe for the treatment of adults with advanced RCC.


Association between occupational exposure and the clinical characteristics of COPD.
The contribution of occupational exposures to COPD and their interaction with cigarette smoking on clinical pattern of COPD remain underappreciated. The aim of this study was to explore the contribution of occupational exposures on clinical pattern of COPD. Cross-sectional data from a multicenter tertiary care cohort of 591 smokers or ex-smokers with COPD (median FEV1 49%) were analyzed. Self-reported exposure to vapor, dust, gas or fumes (VDGF) at any time during the entire career was recorded. VDGF exposure was reported in 209 (35%) subjects aged 31 to 88 years. Several features were significantly associated with VDGF exposure: age (median 68 versus 64 years, p < 0.001), male gender (90% vs 76%; p < 0.0001), reported work-related respiratory disability (86% vs 7%, p < 0.001), current wheezing (71% vs 61%, p = 0.03) and hay fever (15.5% vs 8.5%, p < 0.01). In contrast, current and cumulative smoking was less (p = 0.01) despite similar severity of airflow obstruction. In this patient series of COPD patients, subjects exposed to VDGF were older male patients who reported more work-related respiratory disability, more asthma-like symptoms and atopy, suggesting that, even in smokers or ex-smokers with COPD, occupational exposures are associated with distinct patients characteristics.


Mental Health Service Users' Experiences of Training Focused on Empowerment: Training Environment and the Benefits of Training.
This qualitative study investigated the mental health service users' (MHSUs') experiences of empowerment training and it was based on individual interviews with 24 MHSUs. Findings showed that MHSUs described the training environment through three dimensions: social interaction, learners' internal resources and the pedagogical execution of training. The training reinforced their positive internal resources, stimulated their inner mind activity and gave meaning to their lives. The knowledge of the training environment helps to build environment, which will support MHSUs' training. Empowerment training could be used to strengthen MHSUs' positive internal resources giving them also a possibility to train their cognitive activities.


The self-organization of lipids and proteins of myelin at the membrane interface. Molecular factors underlying the microheterogeneity of domain segregation.
The advances over the last 10 years on the understanding of myelin heterogeneity are reviewed. The main focus is on the applicability of Langmuir monolayers, Langmuir-Blodgett films and some associated techniques to unravelling the behaviour of interfaces formed with all the components of a natural membrane. Lipid-protein lateral segregation appears as a major driving force to determine surface patterns that can change under compression from circular domains to two-dimensional fractal structures. The major proteins of the myelin membrane induce lateral segregation in an otherwise homogeneous surface formed by the mixture of total myelin lipids. The lipid and protein components appear to distribute in the surface domains according to their charge, compressibility and relative molecular weight: myelin proteins, ganglioside GM1 and fluorescent lipid probes partition into liquid-expanded phase domains; other components such as phosphatidylserine and galactocerebroside partition into another liquid phase enriched in cholesterol. Simplified protein-lipid mixtures allow assessment of the participation of the major proteins in the two dimensional pattern development. One of the major myelin proteins, the Folch-Lees proteolipid, self-segregates into, and determines formation of, fractal-like patterns. The presence of the second major protein, myelin basic protein, leads to round liquid-expanded domains in the absence of Folch-Lees proteolipid and softens the boundaries of the fractal structures in its presence. The location of myelin basic protein in the interface is surface pressure sensitive, being slightly squeezed out at high surface pressure, allowing the fractal domains enriched in Folch-Lees proteolipid to evolve.


Design, production and optimization of solid lipid microparticles (SLM) by a coaxial microfluidic device.
This paper describes a method for the production of lipid microparticles (SLM) based on microfluidics using a newly designed modular device constituted of three main parts: a temperature control, a co-flow dripping element and a congealing element. The presented data demonstrated that the microfluidic approach resulted in the production of SLM with narrow size distribution and optimal morphological characteristics in term of sphericity, surface smoothness and absence of defects (i.e. partial coalescence or irregular shape). The optimization of SLM production was performed by screening the effect of different experimental parameters and device configurations by a classical intuitive approach COST (Changing One Separate factor a Time). This process allowed selecting the proper value for a number of parameters including, (i) the congealing element geometry, (ii) the presence and concentration of a stabilizer, (iii) the temperature of water and oil phases and (iv) the water and oil flow rates. In addition, the interplay between oil phase and water phase flow rates, in controlling the size and morphology of SLM, was investigated by a statistical "Design of the Experiments" approach (DoE). The combined use of COST and DoE studies allowed the production of optimized SLM for the encapsulation of dye/drugs. The obtained results demonstrated that the guest molecules did not affect the general characteristics of SLM, confirming the robustness of the microfluidic procedure in view of the production of SLM for biopharmaceutical and biotech protocols.


Post-thyroidectomy hypocalcemia is related to parathyroid dysfunction even in patients with normal parathyroid hormone concentrations early after surgery.
Hypocalcemia may develop even in the presence of normal postoperative parathyroid hormone (PTH) concentrations. We aimed to identify risk factors of hypocalcemia in patients with normal PTH concentration early after total thyroidectomy (TT). We included 1,504 consecutive patients who underwent TT between January 2012 and December 2013. Significant hypocalcemia was defined as serum calcium concentrations of <8.0 mg/dL. Overall, 333 patients had subnormal PTH 4 hours after surgery (4-hour PTH; <10 pg/mL) and received oral calcium (OC) and calcitriol supplementation. Among the 1,171 patients with normal 4-hour PTH (≥ 10 pg/mL; euparathyroid), 211 experienced hypocalcemia and required OC administration. Among the euparathyroid patients, no difference was found between normocalcemic and hypocalcemic patients in terms of age, hormonal status, preoperative PTH, 25-hydroxy vitamin D (25OH-VD), magnesium, and phosphate concentrations. On univariate analysis, euparathyroid hypocalcemic patients were more frequently females, had significantly lower preoperative serum calcium and 4-hour PTH concentrations, and greater decreases in PTH. Independent risk factors for hypocalcemia with normal 4-hour PTH were preoperative serum calcium concentration and PTH decline of ≥ 50%. Female sex, toxic goiter, and 25OH-VD deficiency are not risk factors for post-TT hypocalcemia. Relative parathyroid insufficiency seems to be the principal mechanism of post-thyroidectomy hypocalcemia, even in patients with normal postoperative PTH concentrations.


Acquired Brown syndrome: report of two cases.
We report 2 cases of acquired Brown syndrome, each associated with a mass in the supranasal area of the involved eye. Meticulous endoscopic surgery of an ethmoidal mucocele in the first case resulted in the recovery of superior oblique muscle function. Imaging studies suggested the presence of an orbital venous malformation in the second case, the clinical course of which was stable, with minimal intermittent diplopia over time.


Differential dephosphorylation of the insulin receptor and its 160-kDa substrate (pp160) in rat adipocytes.
A permeabilized rat adipocyte model was developed which permitted an examination of: 1) insulin receptor autophosphorylation, 2) phosphorylation of a putative insulin receptor substrate of 160 kDa, pp160, and 3) the dephosphorylation reactions associated with each of these phosphoproteins. Rat adipocytes, preincubated with [32P]orthophosphate for 2 h, were exposed to insulin (10(-7) M) at the time of digitonin permeabilization. Phosphorylation of pp160 and autophosphorylation of the insulin receptor increased as a function of Mn2+ concentration in the media with near maximum responses at 10 mM. Maximum response was at least as large as the intact cell response to 10(-7) M insulin. In contrast, magnesium did not increase phosphorylation of pp160 although an increase in receptor autophosphorylation was observed. Autophosphorylation was preserved at digitonin concentrations of 20-100 micrograms/ml, but pp160 phosphorylation was negligible beyond 40 micrograms/ml. Our previous work demonstrated that the insulin receptor was associated with a phosphotyrosine phosphatase activity in permeabilized adipocytes (Mooney, R., and Anderson, D. (1989) J. Biol. Chem. 264, 6850-6857). The current permeabilized adipocyte model made possible an examination of the effects of phosphotyrosine phosphatase inhibitors, including several divalent metal cations (Zn2+, Co2+, and Ni2+), vanadate, and molybdate on both net phosphorylation of pp160 and autophosphorylation of the insulin receptor. Zn2+ at 100 microM, Ni2+ at 1 mM, and Co2+ at 1 or 5 mM increased insulin-dependent phosphorylation of pp160 at least 5-fold and autophosphorylation 2-fold. At higher concentrations of Zn2+ (1 mM) and Ni2+ (5 mM), however, no increase in phosphorylation of pp160 was observed and autophosphorylation was inhibited. Vanadate (1 mM) and molybdate (100 microM) increased insulin-dependent phosphorylation of pp160 by 3-fold when tested separately and 7-fold in combination. Insulin receptor autophosphorylation was increased 50% by each and 3-fold when the agents were combined. Dephosphorylation of pp160 and the insulin receptor was analyzed directly by permeabilizing prelabeled insulin-treated adipocytes in the presence of EDTA (10 mM). Dephosphorylation of pp160 was especially rapid with a t1/2 of approximately 10 s. The t1/2 for the insulin receptor was 37 s. Zn2+ at 1 mM (a concentration that inhibited the insulin receptor kinase) was a strong inhibitor of dephosphorylation, prolonging the rate of pp160 dephosphorylation more than 12-fold and insulin receptor dephosphorylation 3-fold.(ABSTRACT TRUNCATED AT 400 WORDS)


Caveolin-1 immuno-expression in human gastric cancer: histopathogenetic hypotheses.
The immunohistochemical expression of caveolin-1 (cav-1) was evaluated in a series of gastric carcinomas (GC) and in the adjacent normal gastric mucosa. Cav-1 immuno-expression was found in most GC (94%) with a significantly higher amount in the Lauren intestinal type in comparison to the diffuse-type carcinomas. Interestingly, gastric intestinal metaplasia as well as the cells at the base and neck of gastric pits within all fundic mucosal fragments showed an evident cav-1 immuno-staining, suggesting a histogenetic derivation of these lesions from the trans-differentiation of chief cells or from a cryptic progenitor population at the base of fundic glands, as recently hypothesized by other authors. The absence of significant correlations between cav-1 immuno-expression and the other clinico-pathological parameters, such as the stage of disease or the patients overall survival, indicates that the role of cav-1 in GC is neither stage-specific nor related to prognosis.


Chemical stimulation of the ventrolateral medullary depressor area decreases ipsilateral cerebral blood flow in anesthetized rats.
In anesthetized (chloralose and urethane), paralyzed and artificially ventilated rats, the neurons in the ventrolateral medullary depressor area (VLDA) were chemically stimulated by microinjections of L-glutamate (2.5-5 nmole in 100 nl of 0.9% sodium chloride solution) and the cerebral blood flow (CBF) was determined using a combination of labeled microspheres (57Co, 113Sn and 46Sc). Unilateral chemical stimulation of the VLDA (n = 11) produced a significant (P less than 0.05) decrease in CBF of the cerebral cortex ipsilateral to the stimulated VLDA; the CBF was 41 +/- 5 (mean +/- S.E.M.) and 29 +/- 4 ml.min-1.(100 g)-1 before and during the chemical stimulation of VLDA. The decrease in CBF was not due to the decrease in arterial blood pressure (ABP) caused by the chemical stimulation of the VLDA because the CBF during the chemical stimulation of the VLDA was significantly smaller (P less than 0.01) than the CBF during controlled hemorrhagic hypotension (n = 10). In another group of rats (n = 6), moderate hypertension was induced by blood transfusion. Unilateral chemical stimulation of the VLDA in these rats decreased ABP but it remained within normotensive range. A significant (P less than 0.05) decrease in CBF (from 46 +/- 12 to 29 +/- 7 ml.min-1.(100 g)-1) and a significant (P less than 0.01) increase in cerebrovascular resistance (from 2.7 +/- 0.4 to 4.3 +/- 0.6 mmHg per [ml.min-1.(100 g)-1]) was observed in the ipsilateral cerebral cortex of these rats. Chemical stimulation of the VLDA did not affect the reactivity of the cerebral vessels to hypercapnea (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)


The influence of early speech rehabilitation with voice prostheses on the psychological state of laryngectomized patients.
This survey assessed how early speech rehabilitation influences the emotional state and psychological adjustment of 43 male laryngectomy patients, at three different chronological stages. The first assessment occurred 2-3 days before the operation. The patients filled out a stress questionnaire (SVF) which assessed coping strategies. Exactly 2 weeks after the operation the patients were given a list of adjectives (EWL) which measured their actual emotional state. One day before leaving the hospital the patients were given the Post-laryngectomy Telephone Test (PLTT) which ascertained the quality of speech intelligibility. In addition, patients filled out a questionnaire on postoperative stress and anticipated stigmatisation with regard to their changed voice. Results demonstrated that patients who had early speech rehabilitation felt significantly more active and, in general, felt considerably better than patients who had not received speech rehabilitation training. Patients assessed voice loss as extremely distressing. The postoperative stress and the anticipated stigmatisation on the basis of the changed voice was significantly higher in those patients with good speech intelligibility than in patients with poor speech articulation at hospital discharge. The coping strategies "Giving up and resignation" and "Need for social support" correlated positively with postoperative stress and anticipated stigmatisation. Results show that early speech rehabilitation with voice prostheses had a positive effect on the emotional state of laryngectomy patients. However, the early speech rehabilitation leads to distress in the initial phase in laryngectomy patients. Moreover, patients who habitually tend towards resignation, or need lots of social support should receive psychological support during the early phase of speech rehabilitation training.


Errors in estimating the orientation of dot patterns.
The error in estimating the orientation of a dot pattern was measured as the difference between the orientation of the least-squared-distances line (LS-line) of the pattern and the orientation of a line adjusted by the subject to match the perceived orientation of the pattern. Analysis of the mean errors (averaged over ten subjects) obtained for one hundred patterns confirmed that the orientation of the LS-line represents the orientation of elongated dot-patterns. It is shown that estimated orientation was systematically biased towards the nearest 45 degrees oblique meridian. This bias points to the importance of the +/-45 degrees directions as natural norms for left- and right-side tilt in the frontoparallel plane.


Failure to demonstrate stimulatory effect of prolactin on vitamin D metabolism in vitamin-D-deficient rats.
The effect of administration of bovine prolactin in vivo on renal 1 alpha-hydroxylase (1 alpha-OHase) activity was investigated using thyroparathyroidectomized and sham-operated vitamin-D-deficient male rats. A high dose (1.5 IU/hr) and a low dose (0.3 IU/hr) of bovine prolactin was constantly infused into the cannulated femoral vein for 6 hr or 30 hr. The accumulation of 1 alpha, 25-hydroxyvitamin D3 [1 alpha, 25-(OH)2-D3] in plasma produced from 25-hydroxy-vitamin D3 (25-OH-D3) was calculated from the 6-hr conversion of intravenously injected [3H]-25-OH-D3 to [3H]-1 alpha, 25-(OH)2-D3. Both high dose and low dose of prolactin administration caused no significant stimulatory effect on 1 alpha-OHase activity in TPTX animals. Also, in sham-operated rats the prolactin treatment produced no significant change in the 1 alpha-OHase activity. Plasma calcium concentrations showed a tendency to increase slightly. These results suggest that prolactin has no direct stimulatory role on renal 1 alpha-OHase activity in rats. Its effect on calcium metabolism may be mediated by a different mechanism(s).


Intramuscular aripiprazole : a review of its use in the management of agitation in schizophrenia and bipolar I disorder.
An intramuscular formulation of the atypical antipsychotic aripiprazole (Abilify) has been developed and is approved in the EU for use in agitation and disturbed behaviour associated with schizophrenia. In the US, it is approved for the treatment of agitation associated with schizophrenia or bipolar I disorder (manic or mixed). In large, well designed trials, intramuscular aripiprazole was an effective and generally well tolerated treatment for agitation associated with schizophrenia, schizoaffective disorder, schizophreniform disorder or bipolar I disorder. Intramuscular aripiprazole was more effective than placebo in these patient populations and was noninferior to intramuscular haloperidol in those with agitation associated with schizophrenia and its related disorders. Aripiprazole is associated with a low risk for extrapyramidal symptoms (EPS), cardiac effects, hyperprolactinaemia, weight gain and other metabolic disturbances. Head-to-head trials comparing intramuscular aripiprazole with other intramuscular atypical antipsychotics are required before the relative position of each of these agents can be fully determined. In the meantime, intramuscular aripiprazole, with its favourable tolerability profile, is a valuable treatment option for agitation in patients with schizophrenia, schizoaffective disorder, schizophreniform disorder or bipolar I disorder.


Sleep deprivation and hippocampal vulnerability: changes in neuronal plasticity, neurogenesis and cognitive function.
Despite the ongoing fundamental controversy about the physiological function of sleep, there is general consensus that sleep benefits neuronal plasticity, which ultimately supports brain function and cognition. In agreement with this are numerous studies showing that sleep deprivation (SD) results in learning and memory impairments. Interestingly, such impairments appear to occur particularly when these learning and memory processes require the hippocampus, suggesting that this brain region may be particularly sensitive to the consequences of sleep loss. Although the molecular mechanisms underlying sleep and memory formation remain to be investigated, available evidence suggests that SD may impair hippocampal neuronal plasticity and memory processes by attenuating intracellular cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling which may lead to alterations in cAMP response element binding protein (CREB)-mediated gene transcription, neurotrophic signaling, and glutamate receptor expression. When restricted sleep becomes a chronic condition, it causes a reduction of hippocampal cell proliferation and neurogenesis, which may eventually lead to a reduction in hippocampal volume. Ultimately, by impairing hippocampal plasticity and function, chronically restricted and disrupted sleep contributes to cognitive disorders and psychiatric diseases.


Molecular epidemiology of drug resistance markers of Plasmodium falciparum malaria in Thailand.
To determine differences in the distribution of drug resistance mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multi-drug resistance 1 (pfmdr1) genes of P. falciparum isolates in Thailand, a study was conducted using polymerase chain reaction-restriction fragment length polymorphism to detect mutations in P. falciparum isolates obtained from three areas with different levels of in vivo mefloquine (MQ) resistance. All isolates carried mutant allele T76 of the pfcrt gene and wild-type allele D1246 of the pfmdr1 gene except for one isolate, which showed the wild-type K76 allele. This isolate was obtained from Chanthaburi Province, an area with high MQ resistance. Relatively low rates of the mutant alleles D1042 and Y86 of the pfmdr1 gene were found among Thai isolates of P. falciparum. However, a statistically significant difference in the distribution was noted. Most of the mutant isolates were found among isolates from areas with moderate or low MQ resistance. Only one isolate with mixed mutant and wild-type N1042 and D1042 and two mutants of Y86 were found among the isolates from areas with high MQ resistance. The findings provide limited support for the hypothesis that mutant alleles of pfmdr1 may be associated with increased sensitivity to MQ.


Decreased LF/HF ratio is associated with worse outcomes in patients who received mechanical thrombectomy under general anesthesia for emergent large vessel occlusion: a retrospective study.
We aimed to determine whether heart rate variability (HRV) was correlated to long-term outcome in patients who received mechanical thrombectomy (MT) under general anesthesia for emergent large vessel occlusion (ELVO). Data from 106 patients receiving MT under general anesthesia to treat ELVO between January 1, 2017 and December 31, 2019 were collected in a multicenter chart review. Univariate analysis, Chi-square test, and bivariate logistic regression were performed to assess the correlations between preoperative risk factors such as HRV and long-term outcome (as indicated by the modified Rankin score [mRS] at 90 days after MT). Bivariate logistic regression revealed that decreased LF/HF (low frequency/high frequency in HRV) ratio was correlated with unfavorable functional outcome as indicated by mRS ≥ 2 (odds ratio [OR], 0.650; 95% confidence interval [CI], 0.157-0.839; p = 0.018), and functionally dependent outcome as indicated by mRS ≥ 3 (OR, 0.704; 95% CI, 0.360-0.914; p = 0.021). It was also found that ELVO in the right anterior circulation was correlated with lower LF/HF ratio, as compared with ELVO in the contralateral side (p < 0.05). Our retrospective study demonstrated that worse outcome in patients with ELVO who received MT under general anesthesia induced autonomic changes and that decreased LF/HF ratio.


Changes in erythrocyte sedimentation rate, white blood cell count, liver enzymes, and magnesium after gastric bypass surgery.
Background. Roux-en-Y gastric bypass (RYGBP) is an established method for treatment of obesity, a condition of chronic inflammation with liver steatosis, characterised by increased erythrocyte sedimentation rate (ESR), white blood cell count (WBC), liver enzymes, and decreased magnesium (Mg). We investigated alterations, if any, in ESR, WBC, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and Mg after RYGBP. Methods. 21 morbidly obese nondiabetic patients who underwent RYGBP surgery were evaluated preoperatively (baseline), then 1 year (1st followup) and 3.5 years (2nd followup) after RYGBP and compared to an untreated control group. Results. Body mass index, ESR, WBC, ALT, and GGT were all significantly reduced at 1 year in the RYGBP group (30%, 35%, 20%, 45%, and 57%, resp.) while Mg increased by 6%, compared to control group (P = 0.001-0.009). Conclusions. Obese patients treated by RYGBP show sustained reductions in ESR, WBC, ALT, and GGT possibly due to reduced liver steatosis and increased Mg.


Na+/H+ exchanger inhibition at the onset of reperfusion decreases myocardial infarct size: role of reactive oxygen species.
A burst of reactive oxygen species and activation of Na+/H+ exchanger take place at the beginning of reperfusion. The aim of this study was to assess the possible interrelation of the inhibition of Na+/H+ exchanger and reactive oxygen species about the determination of myocardial infarct size. Isolated rat hearts were submitted to 40 min of coronary occlusion and 2 h of reperfusion. Infarct size was determined through triphenyltetrazolium chloride staining technique and was expressed as a percentage of risk area. Lipid peroxidation, as a marker of oxidative stress, was estimated by the concentration of thiobarbituric reactive substances. Treatment during the first 20 min of reperfusion with a selective inhibitor of Na+/H+ exchanger 1 isoform, HOE 642 (cariporide; 10 microM), significantly diminished infarct size (15.1+/-2.4% vs. 31+/-2% in untreated hearts). The administration of a "scavenger" of hydroxyl radical, N-(2-mercaptopropionyl)-glycine (2 mM), decreased infarct size in an extent similar to that of cariporide (18+/-3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17+/-1.7%). Each intervention [HOE 642 or N-(2-mercaptopropionyl)-glycine] and its combination improved the postischemic recovery of myocardial systolic and diastolic functions in a similar extent. The content of the thiobarbituric reactive substances of untreated hearts (1012+/-144 nmol/g) decreased to 431+/-81, 390+/-82, and 433+/-41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively. The present data support the conclusion that the cardioprotective effect of cariporide is associated with diminution of oxidative stress.


Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies.
Studies on use of selective serotonin reuptake inhibitors (SSRIs) and risk of fracture have yielded inconsistent results. This meta-analysis, which pooled results from 13 qualifying cohort and case-control studies, found that SSRIs were associated with a significantly increased risk of fractures. This study was conducted to assess whether people who take SSRIs are at an increased risk of fracture. We conducted a meta-analysis of observational studies. Relevant studies published by February 2010 were identified through literature searches using MEDLINE (from 1966), EMBASE (from 1988), PsycINFO (from 1806), and manual searching of reference lists. Only cohort or case-control studies that examined the association of SSRIs and risk of fracture and bone loss were included. Data were abstracted independently by two investigators using a standardized protocol; disagreements were resolved by consensus. Random effects models were used for pooled analysis due to heterogeneity in the studies. Thirteen studies met inclusion criteria. Overall, SSRI use was associated with a significantly increased risk of fracture (relative risk, RR, 1.72; 95% CI [1.51, 1.95]; P < 0.001). An increased fracture risk associated with SSRIs also was observed in the three studies that adjusted for bone mineral density (RR, 1.70; 95% CI [1.28, 2.25]; P < 0.001) and in the four studies that adjusted for depression (RR 1.74; 95% CI [1.28, 2.36]; P < 0.001). SSRI use was not associated with bone loss in the two cohort studies of women (P = 0.29). The overall association between SSRI use and fracture risk was weaker (RR, 1.40; 95% CI [1.22, 1.61]), though still significant (P < 0.001) in analyses that accounted for apparent publication bias. Use of SSRIs is associated with increased risk of fracture. The SSRIs may exert an increased risk of fracture independent of depression and bone mineral density.


An unusual case of uterine tube cancer (transitional cell carcinoma) co-existing with appendicitis: a case report.
The authors present an exceptional case of a transitional cell carcinoma of the uterine tube in a 59-year-old female patient, co-existing with appendicitis. Originally, the patient was assigned to surgery due to an inflamed tumour of the right adnexa. A mid-surgery diagnose revealed appendicitis by chance, but in the course of an examination of the right uterine tube, performed on the spot, no progressive carcinoid process was univocally diagnosed. Therefore, the treatments applied were a bilateral salpingectomy and appendectomy. In the course of the final pathomorphological examination, using an immunohistochemical technique, a primary cancer of the uterine tube composed of transitional epithelium cells (transitional cell carcinoma G-2, pT1a) was diagnosed. At the time of the second surgery, a radical hysterectomy, bilateral oophorectomy and omentectomy were performed and afterwards, the patient was treated with a post-operational radiotherapy. The authors support the thesis that a primary cancer of the uterine tube may, as it looks, suggest a different ailment and present diagnostic problems.


Characteristics of rapid eye movement production during REM sleep in man: organization and rhythmicity.
The purpose of this study was to verify statistically the existence of certain characteristics of rapid eye movement (REM) production during REM sleep: organization and rhythmicity. REM data were collected intermittently, over a period of 20 consecutive nights, from 6 normal adult subjects of both sexes. Results concerning the organization of REM production revealed the presence of 3 evolving slow trends: quadratic, linear and quasi-sinusoidal. The occurrence of a given trend type was not related to subject, night, time of night or length of REM sleep phase being analysed. Results of the analysis showed that it is possible for a series of REMs to contain one, two or more statistically significant rhythmic periods, or no significant rhythmic period. The rhythmic periods that were detected ranged from 1 to 21 min, and no predominant periods were present. As in the case of the slow trends, the occurrence of a given rhythmic period was not dependent on subject, night, time of night or length of the REM sleep phase.


CDC20 promotes radioresistance of prostate cancer by activating Twist1 expression.
Currently, radiotherapy is one of the most attractive treatments for prostate cancer (PCa) patients. However, radioresistance remains a challenging issue and the underlying mechanism is unknown. Growing evidence has demonstrated that CDC20 (Cell division cycle protein 20) plays a pivotal role in a variety of tumors, including PCa. Here, GEPIA database mining and western blot analysis showed that higher expression of CDC20 was observed in PCa tissues and cells. We demonstrated that the expression of CDC20 was increased in PCa cells by irradiation, and knockdown of CDC20 resulted in inhibition of cell proliferation, migration, tumor formation, induced cell apoptosis and increased radiosensitivity in PCa in vitro and in vivo. Furthermore, we observed that CDC20 regulated Twist1 pathway, influencing cell proliferation and migration. These results suggest that targeting CDC20 and Twist1 may be an effective way to improve the radiosensitivity of PCa.


Multi-link endoscopic manipulator robot actuated by shape memory alloys spring actuators controlled by a sliding mode.
The aim of this study was to design and evaluate a prototype of a snake-like endoscopic manipulator robot (SLEMR) and its corresponding automatic controller based on the first order sliding mode theory. The SLEMR was controlled with a set of actuators made of shape memory alloys (SMA). The SLEMR device was constructed with a sequential arrangement of links interconnected by a two degree-of-freedom joint. A parallel agonist-antagonist configuration of actuators was implemented to move each joint. The physical relation between temperature and elongation in SMA forced the execution of the movement in the joint. Elongation-temperature model of the SMA actuator served to get a feasible bound of velocity for each joint. Each pair of SMA actuators was controlled by a first order sliding mode controller. This control design solved the tracking trajectory problem for each joint in the SLEMR because of its robustness against uncertainties and external perturbations. The control action was projected into a feasible implementable set of pulse-width modulated signals which was used to regulate the temperature of the corresponding SMA actuator. The controller designed in this study was experimentally validated in a SLEMR made up by a tridimensional printing technique. The control strategy induced the successful trajectory tracking for all the joints in the SLEMR simultaneously. This characteristic of the control design also enforces the tracking of a reference position by the tip of the final link of the SLEMR. An image acquisition system was used to determine the position of the final actuator in the SLEMR. The effectiveness of the controller proposed in this study was confirmed by the evaluation of the tracking error of the final actuator which approached to a bounded region (less than 1.0 mm) near the origin in a finite-time (0.5 s).


The dog-ear flap as an alternative for breast reconstruction in patients who have already undergone a DIEAP flap.
Breast reconstruction in patients who have previously undergone deep inferior epigastric artery perforator flap (DIEAP) reconstruction or abdominoplasty is often challenging. Depending on patients' body habitus, several second-choice flaps have been described such as the transverse upper gracilis (TUG) flap, profundus femoris artery perforator (PFAP) flap, superior gluteal artery perforator (SGAP) flap, and lumbar artery perforator (LAP) flap. Patients who have undergone a DIEAP flap reconstruction or abdominoplasty occasionally present with dog ears on both sides of the abdominal scar. The adipose tissue and skin of these dog ears are supplied by perforators of the deep circumflex iliac artery (DCIA). The DCIA flap was first described in 1979 by Taylor. We introduce this abdominal "dog-ear" flap for autologous breast reconstruction.


[Amyotrophic lateral sclerosis and frontotemporal dementia-On the way to common gene-specific treatment approaches].
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share common neuropathological features and in the case of a gene mutation, also a genetic cause. To date five ALS-FTD genes are described in the literature in addition to other rare variants. The current state of research on treatment options for ALS and FTD is presented and an outlook on possible gene-specific approaches for ALS-FTD is provided. Analysis of the progression of ALS and FTD research by considering the increasing state of knowledge on the underlying pathomechanisms of the diseases. In addition to anti-inflammatory approaches and stabilization of protein folding, promising gene-specific treatment approaches are currently being developed, which target common causes of ALS and FTD and therefore have an effect on both diseases. So far there are no causal treatment options for ALS and FTD. The increasing importance of genetic causes directs the focus to the development of gene-specific treatment.


Advanced magnetic resonance imaging in pediatric multiple sclerosis.
This review summarizes results from studies that have applied advanced magnetic resonance (MR) imaging techniques to patients with pediatric-onset multiple sclerosis (MS), and includes a discussion of cortical imaging techniques, volumetry, magnetization transfer and diffusion tensor imaging, proton magnetic resonance spectroscopy, and functional MR imaging. Multicenter studies on the sensitivity of these techniques to natural history of disease and treatment response are required before their implementation into clinical practice.


Influenza virus-host interactomes as a basis for antiviral drug development.
Currently, antiviral drugs that target specific viral protein functions are available for the treatment of influenza; however, concern regarding the emergence of drug-resistant viruses is warranted, as is the urgent need for new antiviral targets, including non-viral targets, such as host cellular factors. Viruses rely on host cellular functions to replicate, and therefore a thorough understanding of the roles of virus-host interactions during influenza virus replication is essential to develop novel anti-influenza drugs that target the host factors involved in virus replication. Here, we review recent studies that used several approaches to identify host factors involved in influenza virus replication. These studies have permitted the construction of an interactome map of virus-host interactions in the influenza virus life cycle, clarifying the entire life cycle of this virus and accelerating the development of new antiviral drugs with a low propensity for the development of resistance.


Injuries caused by scorpionfishes (Scorpaena plumieri Bloch, 1789 and Scorpaena brasiliensis Cuvier, 1829) in the Southwestern Atlantic Ocean (Brazilian coast): epidemiologic, clinic and therapeutic aspects of 23 stings in humans.
Fishes of the family Scorpaenidae are responsible for severe injuries and occasionally deaths in humans around the world. The more venomous fishes on the Brazilian coast and in the Southwestern Atlantic region are classified in the genus Scorpaena (family Scorpaenidae). However, there are few studies on the venomous apparatus, the effects of the venom, or clinical aspects of human envenoming provoked by Atlantic scorpionfishes. In this communication, the authors present 23 accidents caused by scorpionfishes of the genus Scorpaena among fishermen, and report the species that provoked the injuries, the circumstances of contacts, the clinical aspects observed and the therapeutic measures utilized for control of the symptoms of the victims. The intense pain and the systemic findings observed in the patients were very frequent and we think that the injuries provoked by scorpionfishes should be considered the most important manifestations caused by venomous fishes of the East Atlantic Ocean.


Highly sensitive detection of cobalt through fluorescence changes in β-cyclodextrin-bimane complexes.
A supramolecular complex of syn-(methyl,methyl)bimane (1) and β-cyclodextrin demonstrates a sensitive (limit of detection = 0.60 nM) and selective fluorescence turn-off response in the presence of cobalt in aqueous media, with calibration curves enabling quantitation in solution and using filter papers on which bimane and cyclodextrin were adsorbed. 1H NMR spectroscopy provides insight into interactions underlying the sensor performance.


Pediatric applications of helical (spiral) CT.
By acquiring a volumetric data set helical CT has advanced many established applications of conventional CT. The most important advantages of helical CT over conventional CT are (1) the shorter examination time, which decreases image degradation from motion artifact, even in infants and young children; (2) the capability for retrospective image reconstruction, which decreases image degradation from volume averaging; and (3) improved multiplanar reconstructions. By reducing motion artifacts and partial volume averaging associated with conventional CT scanning, helical CT reduces the number of repeat CT sections and ultimately the radiation exposure. Helical CT also provides the potential for new applications of CT, such as dynamic studies of pulmonary physiology. Continued clinical experience will advance the pediatric applications of helical CT in the evaluation of thoracic, abdominal, and musculoskeletal pathology. Because of its advantages over conventional CT, helical CT has the potential to become the preferred method of CT imaging in children.


Acetophenones from Acronychia pedunculata and their Cancer Chemopreventive Activity.
From the roots of Acronychia pedunculata (L.) Miq. (Rutaceae) collected in Taiwan, six known and three new acetophenones have been isolated. The new compounds were named acrophenones D (1), E (2), and F (3). Of the acetophenones isolated in this study, prenylacronylin (4) and acronyculatin D. (10) exhibited significant inhibitory activity against 12-0-tetradecanoylphorbol 13-acetate-induced Epstein-Barr virus early antigen activation in Raji cells.


An anthropometric study of the external ear in the Thai population.
Auricular dimensions are important data for the treatment of auricular deformities, either congenital or acquired. Many previous studies have shown that the auricular dimension varies among ethnic groups; however, there are currently no available data for the Thai population. The objective of this investigation was to provide normative values regarding the adult ear dimensions in Thailand. A total of 200 Thai volunteers between the ages of 18 and 70 years (80 men, 120 women) were enrolled in this study. We measured six dimensions, including the auricular, lobular, and conchal length and width and the auricular projection at the superaurale and tragal levels. Moreover, we calculated the auricular, lobular, and conchal indices. The selected dimensions of the external ears were shown as means ± standard deviations. These parameters were then compared between the right and left sides, men and women and participants aged ≥50 and <50 years. We found that men have a significantly larger and more projected ear than women do. The length of the entire auricles and the length of the earlobe were also significantly longer in the population ≥50 years than those <50 years. This study provides normative data of the external ear dimension and projection in the adult Thai population. These data can be used to reconstruct the ear and face more appropriately for Thai individuals.


Osseointegrated implants is a surgical treatment permitting a direct skeletal attachment of an external prosthesis. It is a treatment for healthy transfemoral amputated patients who cannot tolerate or use a socket prosthesis, thereby alleviating related issues with poor fit, skin problems or discomfort. This review provides a summary of the indications and contraindications for surgery, the most common implants and reported outcomes.


Exploration of the clinical course of frozen shoulder: A longitudinal multicenter prospective study of functional impairments.
Contradictory evidence exists regarding the clinical course of frozen shoulder (FS). To explore the clinical course of FS regarding disabilities, pain, range of motion (ROM), muscle strength, scapular upward rotation, and proprioception and to establish longitudinal correlations between these variables. Patients with FS were prospectively followed for 9 months at 3-month intervals. Assessment included the Disabilities of the Arm, Shoulder and Hand questionnaire; visual analogue scale for pain; an inclinometer for shoulder external rotation (ER), internal rotation (IR), flexion, and abduction ROM, and scapular upward rotation and proprioception, as well as handheld dynamometry for muscle strength in shoulder abduction, ER, and IR. Initially, 149 patients (98 females; mean (SD) age 53 (9) years) were included, with 88 completing all follow-up assessments. Most variables showed early improvement in the clinical course of FS, particularly ER and IR at 90° abduction, which continued to improve from 6 to 9 months of follow-up. Associations were observed between disabilities and pain (r = 0.61), disabilities/pain and ROM (r=-0.62 to -0.59 and r=-0.47 to -0.39, respectively), disabilities/pain and muscle strength (r=-0.24 to -0.35 and r=-0.36 to -0.17, respectively), and between disabilities/pain and scapular upward rotation below shoulder level (r = 0.23 to 0.38 and r = 0.24 to 0.30, respectively). ROM correlated with muscle strength (r = 0.14 to 0.44), while both ROM and ER muscle strength correlated with scapular upward rotation below shoulder level (r=-0.37 to -0.23 and r=-0.17 to -0.12, respectively). Muscle strength correlated with scapular upward rotation above shoulder level (r = 0.28 to 0.38) and lift-off muscle strength correlated with joint repositioning (r=-0.17 to -0.15). Almost all factors improved in the early phase (3-6 months) after baseline assessment, while ER and IR ROM at shoulder level continued to improve long term.


A large outbreak of Shigella sonnei gastroenteritis associated with consumption of fresh pasteurised milk cheese.
A large outbreak of Shigella sonnei gastroenteritis occurred in Murcia Region (Southeast Spain) in the winter of 1995-1996. More than 200 people were affected. Epidemiological investigations implicated a regionally manufactured fresh pasteurised milk cheese as the vehicle of infection. A case-control study showed a statistically significant association between the illness and consumption of the suspect cheese. The dispersed sale of the cheese resulted in a regional dissemination of the organism and people were affected in eight townships. Research suggested that an infected foodhandler at the cheese factory might have been the source of contamination and that the processing method might have allowed cross-contamination to occur. This study emphasises the importance of increasing the control of strict hygiene during the processing of fresh cheese, since legislation does not forbid direct contact by hand that could result in contamination of cheese even when the milk pasteurisation process was correctly performed.


[Who is the user of socio-health interventions and what are their needs?].
Socio-health interventions include performance and care intended to attend to the needs of people who have suffered a decrease in their personal autonomy because of their age, illness or disability. Oriented towards achieving an improvement in the quality of life of people in that situation, they try to meet the requirements of people in an integrated way. To intervene in those situations involves providing technical aids and environmental, custom and social changes as well as personal care needed to improve their quality of life and enhance their skills and well-being. Scientific advances and demographic and social changes have determined a change in the profile of socio-health interventions' receivers, highlighting longevity, chronicity of processes and aging of the informal caregiver. The aim of this work is to characterize the person receiving the social-health interventions and to reflect on what their needs are. To do this we have conducted a biomedical studies' review through literature searches at ScienceDirect as well as a review of national institutional documentation related to people in dependent situations and their family caregivers. People who need socio-health help establish a heterogeneous population in respect of their needs. Both the person with disabilities and their informal caregiver need to be considered as an object of interest and attention.


High-speed vascular dynamics of the hemodynamic response.
While a range of cellular mechanisms have been proposed to underlie control of neurovascular coupling, a comprehensive, reconciliatory model has yet to be determined. To fit with such a model, it is essential that candidate mechanisms exhibit reaction times, spatial ranges, and speeds of propagation that are consistent with the vascular manifestations of the 'hemodynamic response'. Understanding these vascular dynamics is therefore a critical step towards developing a robust model of neurovascular coupling. In this study, we utilize high-speed optical imaging of exposed rodent somatosensory cortex to explore and characterize the spatiotemporal dynamics of surface vessels during functional hyperemia. Our high-speed, high-resolution optical imaging approach allows us to study the hemodynamic response independently in individual vessels, and in discrete regions of the parenchyma with enough resolution to precisely characterize subtle spatial and temporal features of the response. Specifically, we explore when and where the first hemodynamic changes occur in response to stimuli, the direction and speed at which these changes propagate in arterioles and regions of the parenchyma, and the relative timing at which each of these compartments returns to its original baseline state. From these results, we are able to conclude that the hemodynamic response appears to initiate in the parenchyma and then spreads rapidly to surface arterioles. Following the initial onset we find evidence that the response spreads spatially outwards via the dilation of targeted arterioles. This propagation of vasodilation is independent of the direction of blood flow within each arteriole. We also find evidence of a decay phase that acts with a more uniform spatial dependence, rather than along targeted vessels, causing the periphery of the responding region to return to baseline first. We hypothesize that different underlying cellular mechanisms/signaling pathways are responsible for the response initiation and the response decay. Our results advance the fundamental understanding of the hemodynamic response, as well as our ability to evaluate potential cellular mechanisms for their involvement in neurovascular coupling.


Rapid inhibition of MAPK signaling and anti-proliferation effect via JAK/STAT signaling by interferon-alpha in hepatocellular carcinoma cell lines.
The potential anti-proliferation effect of interferon-alpha (IFN-alpha) against hepatocellular carcinoma (HCC) and its growth inhibitory mechanisms remain unclear. We examined four human HCC cell lines and every cell line had the anti-proliferative effect of IFN-alpha. The PLC/PRF/5 cell line, which expressed the IFN receptor most abundantly, responded most effectively to IFN-alpha stimulation. Here, we delineate the anti-proliferative effect of IFN-alpha via the MAPK pathway in human HCC cell lines. IFN-alpha retarded G1/S transition with no evidence of apoptosis and inhibited cell proliferation. IFN-alpha diminished the phosphorylation of both extracellular signal-regulated kinase (ERK) and mitogen-activated ERK-regulating kinase (MEK), but not Raf, within 5 min. Knockdown of signal transducers of activation and transcription1 (STAT1) or Janus kinase1 (JAK1) suppressed the reduction of phosphorylation both of ERK and MEK and diminished the growth inhibition by IFN-alpha. These results suggest that IFN-alpha induces anti-proliferative signaling via the JAK/STAT pathway downstream of IFN-alpha receptors and may reduce the growth stimulation signaling by cross-talk with the MEK/ERK pathway without IFN-alpha-induced transcription.


Ornate, large, extremophilic (OLE) RNA forms a kink turn necessary for OapC protein recognition and RNA function.
Ornate, large, extremophilic (OLE) RNAs represent a class of noncoding RNAs prevalent in Gram-positive, extremophilic/anaerobic bacterial species. OLE RNAs (∼600 nt), whose precise biochemical functions remain mysterious, form an intricate secondary structure interspersed with regions of highly conserved nucleotides. In the alkali-halophilic bacterium Bacillus halodurans, OLE RNA is a component of a ribonucleoprotein (RNP) complex involving at least two proteins named OapA and OapB, but additional components may exist that could point to functional roles for the RNA. Disruption of the genes for either OLE RNA, OapA, or OapB result in the inability of cells to overcome cold, alcohol, or Mg2+ stresses. In the current study, we used in vivo crosslinking followed by OLE RNA isolation to identify the protein YbxF as a potential additional partner in the OLE RNP complex. Notably, a mutation in the gene for this same protein was also reported to be present in a strain wherein the complex is nonfunctional. The B. halodurans YbxF (herein renamed OapC) is homologous to a bacterial protein earlier demonstrated to bind kink turn (k-turn) RNA structural motifs. In vitro RNA-protein binding assays reveal that OLE RNA forms a previously unrecognized k-turn that serves as the natural binding site for YbxF/OapC. Moreover, B. halodurans cells carrying OLE RNAs with disruptive mutations in the k-turn exhibit phenotypes identical to cells lacking functional OLE RNP complexes. These findings reveal that the YbxF/OapC protein of B. halodurans is important for the formation of a functional OLE RNP complex.


The potential impact of a cataract surgery programme on the care of orphans and vulnerable children in Swaziland.
We aimed to evaluate the potential impact of a cataract surgery programme at the Good Shepherd Hospital, Siteki, Swaziland, on the care of orphans and vulnerable children in Swaziland. We studied consecutive patients aged 50 years and older undergoing surgery for age-related cataract who reported having children living in their household. Of 131 subjects recruited, 65 (49.6%) were the primary caregivers for the child(ren) in their household. Visual acuities measured 2 weeks after surgery significantly improved. Four weeks after surgery, there was a sizable increase in the proportions of subjects who were able to undertake self-care activities, attend to activities of daily living, undertake income-generating activities and care for children. Cataract surgery on elderly visually impaired patients has the potential to impact positively on the care of orphans and vulnerable children.


Early-life exposure to methylmercury in wildtype and pdr-1/parkin knockout C. elegans.
We examined the impact of early-life exposure to methylmercury (MeHg) on Caenorhabditis elegans (C. elegans) pdr-1 mutants, addressing gene-environment interactions. We tested the hypothesis that early-life exposure to MeHg and knockout (KO) of pdr-1 (mammalian: parkin/PARK2) exacerbates MeHg toxicity and damage to the dopaminergic (DAergic) system. pdr-1KO worms showed increased lethality and decreased lifespan following MeHg exposure. Mercury (Hg) content, measured with inductively coupled plasma-mass spectrometry was increased in pdr-1KO worms compared to wildtype (N2) controls. 2'7' dichlorodihydrofluorescein diacetate assay revealed a significant increase in reactive oxygen species in both strains following MeHg exposure; however, while N2 worms showed an increase in skn-1 transcript levels following MeHg exposure, there was no difference in skn-1 induction in pdr-1KO worms. Dopamine-dependent behavioral analysis revealed an effect of MeHg on N2 wildtype worms, but no effect on pdr-1KO worms. Taken together, these results suggest that pdr-1KO worms are more sensitive to MeHg than wildtype worms, but MeHg does not exacerbate behavioral changes related to the absence of pdr-1.


Bendamustine as salvage treatment in patients with advanced progressive breast cancer: a phase II study.
A phase II pilot study of bendamustine as salvage treatment in patients with advanced breast cancer was performed to determine the objective response rates and make further observations on the toxicity of this drug. A group of 37 patients, pretreated with chemotherapy for advanced disease, entered the trial. Treatment consisted of 150 mg/m2 bendamustine on days 1 and 2 of a 4-week treatment course. Patients continued to receive treatment until complete remission and then two further courses, until tumour progression or unacceptable toxicity ensued. A total of 36 patients received at least one treatment course and were assessable for toxicity; 33 patients were evaluable for treatment results. Dose-limiting grade 3 and 4 WHO toxicity occurred in 5 and 3 patients respectively; 27% of patients entered complete or partial tumour remission. The median time to tumour progression was 2 months with a range of 1-14 months. The efficacy of bendamustine was apparently independent of pretreatment with anthracyclines, suggesting a lack of cross-resistance between bendamustine and anthracyclines. It can be concluded that bendamustine in the dose and application schedule used here is active in the salvage therapy of women with advanced breast cancer. The toxicity was acceptable. Future studies have to confirm the data of this pilot trial and to define the role of bendamustine in the combination chemotherapy of metastatic breast cancer that has been suggested by previous trials.


Hyperglycemia induces corneal endothelial dysfunction through attenuating mitophagy.
Hyperglycemia increases the risk of corneal endothelial dysfunction, resulting in damage to corneal endothelial structure and function. However, the effect and mechanism of hyperglycemia-induced corneal endothelial damage remain elusive. In this study, we demonstrated that hyperglycemia reduced the expression of pump-related protein Na+/K+ ATPase and barrier-related protein ZO-1. Moreover, we found hyperglycemia caused abnormal changes of morphological mitochondria and dynamics in vitro. In addition, the decreased levels of mitophagy were further confirmed Western blotting and LC3B-Mitotracker Immunofluorescence. Exogenous application of mitophagy agonist carbonyl cyanide m-chlorophenyl hydrazine (CCCP) increases the expression of Na+/K+ ATPase and ZO-1 in corneal endothelial cells through up-regulated mitophagy in vitro. In addition, CCCP effectively reverses the phenomenon of corneal opacity and increased corneal thickness in diabetic mice. Therefore, our demonstrated the novel function of mitophagy in the pathogenesis of diabetic cornea endothelial dysfunction, and provide potential approach for treating diabetic corneal endothelial dysfunction.


Identification of 9-hydroxylamine-1,2,3,4-tetrahydroacridine as a hepatic microsomal metabolite of tacrine by high-performance liquid chromatography and electrochemistry.
Amperometric detection using a dual-electrode thin-layer cell in the series configuration can aid in the identification of unknown components in complicated samples by voltammetric characterization. This is shown by studying the metabolism of tacrine by rat hepatic microsomes using high-performance liquid chromatography with electrochemical detection. The major metabolite detected in microsomal incubations did not co-elute with any standard acridine available and was produced in too small a quantity for mass spectral characterization. Tentative identification of this metabolite as 9-hydroxylamine-1,2,3,4-tetrahydroacridine was made by electrochemical characterization. The electrochemistry of the metabolite was compared to that of the hydroxylamine produced and studied by cyclic voltammetry.


One hundred consecutive coarctation resections followed from one to thirteen years.
The technique of operative repair for coarctation of the aorta is now well standardized and the immediate surgical mortality has been lowered to less than 5% in most large series. Long term follow up, however, is only recently being reported. This paper describes the current status of 100 consecutive patients who underwent elective resection from 1--13 yr ago. There was only one operative death. In contrast with other reports, residual systemic hypertension is rare in the 97 survivors. These observations confirm that coarctation of the aorta can be repaired surgically with an acceptable operative mortality; the outlook of the survivors appears excellent.


Upper gastrointestinal diseases in patients for endoscopy in South-Western Uganda.
There is a paucity of published data regarding upper gastrointestinal diseases in Ugandans with upper gastrointestinal symptoms referred for endoscopy. To study the presenting complaints, pathology and Helicobacter pylori prevalence among patients with upper gastrointestinal symptoms in South-Western Uganda. Patients presenting with upper gastrointestinal symptoms underwent upper endoscopy and a urease test for Helicobacter Pylori, all suspicious lesions were biopsied for histopathology review as appropriate. The most common presenting complaints were epigastric pain (51.6%), dysphagia (13.6%) and odynophagia (7.1%). The most common endoscopy finding was gastritis (40.2%), followed by normal examination (15.2%), oesophageal cancer (13.6%), gastric ulcer (7.6%) and gastric cancer (7.1%). Patients older than 40 years (n=110) had significant findings including gastritis (50.9%), oesophageal cancer (22.7%) and gastric cancer (11.8%). However in younger patients, with the age range of 18-40 years (n=74), most examinations were normal (92.9%). Of the 176 patients able to undergo Helicobacter pylori testing 75.6% were positive. Helicobacter pylori infection was associated with statistically significant increase in gastritis, oesophageal cancer, gastric ulcer, gastric cancer, and duodenal ulcers (p-values< 0.05). Gastritis, ulcerative disease, and upper gastrointestinal malignancies are common in South-Western Ugandans and are associated with a high prevalence of Helicobacter pylori.


Application of high-performance liquid chromatofocusing to the study of prostatic androgen receptors. Effect of stabilizing agents on the heterogeneity of receptor structure.
Cytosolic androgen receptors from normal rat prostate were analyzed by high-performance liquid chromatofocusing. Two ion-exchange columns, AX-300 and AX-500, and two equilibration systems, Tris-HCl and imidazole-HCl, were used. pH gradients ranged between 8.3 and 3.5 for Tris-HCl and from 7.7 to 3.5 for imidazole-HCl. In the absence of sodium molybdate and inhibitors of proteolytic enzyme, six specific radioactive fractions (pH: 7.9, 7.7, 7.0, 5.1, 4.7 and 4.4) were eluted from AX-300 equilibrated with Tris-HCl in a ratio of 28:20:52 for acidic, intermediary and basic forms, respectively; similar results were obtained with AX-500 although this column was less effective in resolving basic forms of the receptor. The buffering capacity of imidazole-HCl was lower than that of Tris-HCl, resulting in a steeper elution pH profile. The resolution between acidic and basic forms was thus diminished and only four specific radioactive fractions at pH 7.2, 7.1, 6.5 and 3.6, were observed on AX-500 in a ratio of 23:10:67 for acidic, intermediary and basic forms. In the presence of sodium molybdate, two acidic fractions were found with Tris-HCl at pH 4.3 and 4.7 (47%) on AX-300, whereas the radioactivity of fractions at pH 7.0 and 5.1 (32%) was considerably lowered and intermediary forms remained unchanged (21%). With imidazole-HCl on AX-500, the peak at pH 7.2 disappeared and the acidic form shifted from pH 3.6 to 4.3. In the presence of inhibitors of proteolytic enzyme and sodium molybdate, specifically bound radioactivity was found mostly in a broad acidic fraction (75%) at pH 4.5 on columns equilibrated with Tris-HCl; radioactivity at pH 7.6 disappeared completely but a small amount (15%) remained at pH 7.9. In imidazole-HCl, a main radioactive fraction was eluted at pH 7.1 and two other fractions were collected at pH 6.8 and 4.3 respectively. In conclusion, multiple forms of the rat prostate androgen receptor were evinced by high-performance liquid chromatofocusing. Tris-HCl proved to be a more efficient equilibration system than imidazole-HCl for the resolution of rat prostate cytosolic binding proteins. Under the experimental conditions used, sodium molybdate and inhibitors of proteolytic enzyme greatly favored the acidic form to the detriment of the intermediary and basic entities.


The Evaluation and Therapeutic Management of Hypertension in the Transplant Patient.
Organ transplantation is the therapeutic option of choice in the appropriate patient with end-organ disease. A major comorbidity after the transplant is the development of hypertension which is a risk factor for cardiovascular disease. Cardiovascular disease is the most common cause of death in this population even when there is a functioning graft. It is essential to evaluate post-transplant hypertension not only in the office setting but at home and at night as well. Hence, the use of 24-h ambulatory blood pressure monitoring in both diagnosis and long-term care of this patient population is paramount. Factors involved in uncontrolled hypertension include the donor, recipient, and those specific to the transplant such as immunosuppressive drug exposure. The major offending immunosuppressive agents belong to the calcineurin inhibitor class. The therapy of post-transplant hypertension involves pharmaceutical and non-pharmaceutical interventions that should be tailored to the specific patient and type of transplant. There is clearly a need for more definitive data and quality studies in both the renal and non-renal transplant populations.


Computer-aided design and manufacturing of bone- and tooth-borne maxillary protraction with miniscrews and Class III elastics: Can we contemporize Class III treatments in growing patients?
The purpose of this clinical report is to illustrate an innovative treatment plan for a patient with Class III malocclusion. The plan combined the versatility of computer-aided design and manufacturing technology with miniscrews. Maxillary and mandibular fully customized metal framework anchored to 4 miniscrews was digitally designed and constructed for a growing patient with midface hypoplasia and a skeletal Class III malocclusion. The patient wore Class III elastics between hooks on the maxillary and mandibular frameworks full time for 10 months. Overcorrection was obtained with limited dental side effects, and a significant improvement of the profile was achieved. With the advantages of computer-aided design and manufacturing technology and less invasive insertion procedure compared with miniplate surgery, this patient-specific treatment approach was simple and effective.


Palladium-Catalyzed Carbonylative Dearomatization of Indoles to Achieve Carbonyl-Containing Spirocyclic Indolenines Bearing an All-Carbon Quaternary Center.
A Pd-catalyzed carbonylative dearomatization via an acyl Pd complex has been developed. Diversified carbonyl-containing spirocyclic indolenines with an all-carbon quaternary center were constructed in an efficient and straightforward way with good to excellent yields. The protocol features a simple catalytic system, operational simplicity, a broad substrate scope, easy scale-up, and versatile transformations. In addition, the asymmetric reaction was initially explored with moderate enantioselectivity.


1,25-dihydroxyvitamin D3 inhibits proliferation of IMR-90 human fibroblasts and stimulates pyruvate kinase activity in confluent-phase cells.
This study tested the hypothesis that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a role in regulating some aspects of metabolism in IMR-90 normal human fetal lung fibroblasts. Among the enzymes studied, only pyruvate kinase showed a significant increase after treatment of confluent-phase cells with 1,25(OH)2D3 at various concentrations (0.1-100 nM range) for 24 h. A parallel increase in lactate output was observed. Steroid specificity was established by the failure of 10 nM levels of 25-hydroxyvitamin D3, estradiol-17 beta and progesterone to affect pyruvate kinase activity. The determination of the time course of [3H]-2-deoxy-D-glucose transport indicated that the hormone did not influence the transmembrane transport system of D-glucose. The addition of the inhibitors cycloheximide and actinomycin D to the culture medium abolished, at least in part, the 1,25(OH)2D3 stimulation of pyruvate kinase activity, suggesting the probable dependence of the hormone effect on cellular RNA and protein synthesis. 1,25(OH)2D3 also affected fibroblast growth and DNA synthesis. Cell number significantly decreased after 2-5 days treatment with 10 nM hormone in comparison with control fibroblasts, and also the incorporation of [3H]thymidine into DNA decreased after treatment of the cells with 1 and 10 nM hormone for 48 h. In conclusion, these data demonstrate that 1,25(OH)2D3 stimulates pyruvate kinase activity in confluent-phase IMR-90 human fibroblasts by a mechanism probably dependent on de novo protein synthesis, and also affects cell growth and DNA synthesis in sub-confluent-phase cells.


Vapor-phase microprinting of multicolor phosphorescent organic light emitting device arrays.
Multicolor electrophosphorescent organic light-emitting diode (OLED) pixel patterning by organic vapor jet printing (OVJP) is demonstrated, showing that this technique is capable of rapidly generating high-definition full-color displays. The resolution limits, and means to achieve them are described using a combination of simulation and experimental approaches.


Burden of sleep disturbance in non-Hispanic Black pregnant women.
Non-Hispanic Black pregnant women disproportionately experience poor perinatal outcomes compared to other racial/ethnic groups. Sleep disruption has emerged as a risk factor for adverse pregnancy outcomes, but there are limited data in minority pregnant women. We examined the prevalence of habitual snoring and its timing of onset with several key sleep-wake disturbances and their associations with perinatal outcomes in a cohort of non-Hispanic Black pregnant women. Non-Hispanic Black pregnant women in their third trimester were recruited from a large academic medical center and screened for habitual snoring and its timing relative to pregnancy, along with sleep quality, symptoms of insomnia, excessive daytime sleepiness, and daytime function. Clinical diagnoses of hypertensive disorders of pregnancy were obtained along with delivery outcomes. In 235 women, the vast majority (80%) reported 3 or more sleep-wake disturbances, and almost half had at least 5 disturbances. Sixteen percent reported prepregnancy snoring and 20% reported pregnancy-onset snoring. Women with pregnancy-onset snoring had significantly increased odds of poor sleep quality (adjusted odds ratio [aOR] = 8.2), trouble staying asleep (aOR = 3.6), waking up too early (aOR = 2.7), excessive daytime sleepiness (aOR = 2.3), and poor daytime function (aOR = 8.7) but no relationship with perinatal outcomes. In contrast, prepregnancy snoring was related to chronic hypertension, preterm delivery, and fetal growth restriction (aOR = 2.6, aOR = 2.8, and aOR = 5.1, respectively). Sleep-wake disturbances confer a significant burden to pregnant non-Hispanic Black women, an infrequently studied yet disproportionately affected population. Contributions of maternal sleep to racial disparities in perinatal health should be a priority for public health research. White KM, Dunietz GL, Pitts DS, Kalmbach DA, Lucchini M, O'Brien LM. Burden of sleep disturbance in non-Hispanic Black pregnant women. J Clin Sleep Med. 2022;18(5):1319-1325.


Novel method for measurement of heparin anticoagulant activity using SPR.
A novel method has been developed for the easy measurement of heparin's anticoagulant activity using surface plasmon resonance. The anticoagulant activity of target heparin was evaluated by measuring the competitive antithrombin III binding of analyte heparin in the solution phase and USP heparin immobilized on chip surface. Heparins, obtained from different animal sources, and low molecular weight heparins were analyzed. The results were reproducible and correlated well with the results of chromogenic assays (correlation coefficient r = 0.98 for anti-Xa and r = 0.94 for anti-IIa). This protocol provides many advantages, significantly minimizing time, cost and the complications of chromogenic assay methods.


Partially saturated fluorinated heterocycles: diastereo- and enantioselective synthesis of β-trifluoromethyl-pyrroline carboxylates.
The first asymmetric synthesis of β-trifluoromethylated pyrroline carboxylates has been achieved by organocatalytic conjugated addition of adamantyl glycine imine to β-trifluoromethylated enones, followed by a deprotection/cyclization/dehydration sequence.


ZD7288 inhibits postsynaptic glutamate receptor-mediated responses at hippocampal perforant path-granule cell synapses.
Hyperpolarization-activated channels (Ih) are widely expressed in the nervous system and believed to play an important role in the regulation of membrane excitability and rhythmic activity. Recent evidence suggests that Ih may be involved in long-term potentiation (LTP) in the hippocampus; however, the results are controversial. To explore the possible causes of these differing results, the effects of Ih blockers on synaptic activity were evaluated in mouse hippocampal slices. ZD7288 (20 micro m), a selective Ih blocker, apparently prevented the induction of LTP, while Cs+ (1 mm), a commonly used Ih blocker, had no effect on LTP at hippocampal perforant path-dentate granule cell synapses. In addition, ZD7288 but not Cs+ abolished basal synaptic transmission. Results from voltage-clamp experiments showed that ZD7288 produced a very little inhibition on hyperpolarization-activated currents, indicating a weak expression of the Ih in granule neurons. Outside-out patch recordings revealed that ZD7288 inhibited glutamate receptor-mediated responses, while Cs+ had no effect on them. Meanwhile, ZD7288 reduced both alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and N-methyl-d-aspartate receptor-mediated excitatory postsynaptic currents. The results suggest that ZD7288-induced reduction of synaptic transmission may result from its inhibition of the postsynaptic glutamate receptors on dentate granule neurons.


[Total knee replacement using the Walldius hinge joint (author's transl)].
45 Walldius knee joints have been reevaluated an average of 3 years after implantation. 75% were considered good to excellent when compared with the preoperative situation. Most failures were due to infection (11%). The end result depends largely on the condition of adjacent joints which frequently prevent a major improvement in walking ability inspite of a successful implantation of a Walldius prosthesis. The Walldius hinge joint was prefered over other designs because of its large weight-bearing flanges. It can absorb static forces better without sinking into the tibial or femoral shafts. Inspite of a resection of 3 cm, a fusion is still possible if necessary. The use of cement is emphasised to prevent migration of the prosthesis and fracture of the shafts. Inspite of a high complication rate the prosthestic replacement of a severely destroyed knee joint by a Walldius hinge is a promising procedure.


Clinicopathological characteristics and survival outcomes in patients with angiosarcoma of breast.
Angiosarcoma of the breast is a rare malignancy. There are little data evaluating the survival and estimating the prognostic factors. The best surgical management and the role of systemic adjuvant therapy remain ill-defined. This study aimed to investigate the clinicopathological features, survival, and prognostic factors of breast angiosarcoma. The data on patients diagnosed with breast angiosarcoma were extracted from the Surveillance, Epidemiology, and End Results database (1975-2016). Univariate and multivariate Cox regression analyses were used to estimate the influential prognostic factors. The overall survival (OS) and disease-specific survival (DSS) of patients with breast angiosarcoma were evaluated. This study included 656 patients diagnosed with breast angiosarcoma between 1975 and 2016. The 5-year OS rate of all patients was 44.9% (95% CI 40.8-49.0). In both OS and DSS, Kaplan-Meier survival analyses revealed significant differences for both OS and DSS according to age, year at diagnosis, laterality, grade, and stage (all log-rank p < 0.05). Multivariate analysis suggested that lesions of the right breast, poor differentiation, and advanced stage were independent risk factors for OS or DSS (all p < 0.05). Older age was a risk factor in OS, but was protective in DSS. In primary breast angiosarcoma, age, laterality, grade, and stage were independent prognostic factors in OS and DSS (all p < 0.05). Mastectomy was also a risk factor in DSS (p = 0.034). The proportion of patients with grade III and regional disease was larger in the mastectomy group. Angiosarcoma of the breast had a poor prognosis. In our study, age, laterality, histologic grade, and stage were identified as significant prognostic factors. Why patients with angiosarcoma of the right breast had a worse prognosis remains equivocal. Mastectomy was adopted more often by surgeons in this cohort study for patients with advanced primary breast angiosarcoma.