[Changes in lipid tissue redistribution and metabolic disorders in HIV positive patients treated with protease inhibitors].
Significant decrease in AIDS mortality rate has been noted since 1996 when proteases inhibitors (PI) were introduced into vast use. Unfortunately they revealed major side effects of which lipodystrophy (L) turned out to be very serious due to various clinical implications consequently worsening prognosis of HIV-positive patients treated with HAART (highly active antiretroviral therapy). Redistribution of lipid tissue in many cases was a reason of switching the PI-therapy, though very effective, into PI-sparing therapy of non-nucleoside reverse transcriptase inhibitors (NNRTI) and nucleoside reverse transcriptase inhibitors (NRTI), doubtlessly confining future therapeutic options. This review presents our to date knowledge on clinical aspects, pathogenesis, treating and further consequences of these changes.


Impact of olfactory dysfunction on quality of life in coronavirus disease 2019 patients: a systematic review.
To outline the impact on quality of life in coronavirus disease 2019 patients with olfactory dysfunction. Five databases were searched for articles referring to the impact on quality of life in coronavirus disease 2019 patients with olfactory dysfunction. The search was conducted for the period from November 2019 to April 2021. The search was conducted over one month (May 2021). Four studies that met the objective were included. Altogether, there were 1045 patients. Various questionnaires were used to assess quality of life. Overall, the quality of life deficit affected 67.7 per cent of patients. Quality of life domains investigated include overall quality of life (four studies), food and taste dysfunction (two studies), mental health (two studies), cognitive function (one study), functional outcome (one study) and safety domains (one study). Quality of life deficit was reported to be 67.7 per cent among coronavirus disease 2019 patients with olfactory dysfunction. The high prevalence of persistent olfactory dysfunction prompts more serious research, as the long-standing consequences of olfactory dysfunction are detrimental.


Mini vs standard percutaneous nephrolithotomy for renal stones: a comparative study.
To compare the outcome of mini-percutaneous nephrolithotomy (Mini-PNL) versus standard-PNL for renal stones. Retrospective study was performed between March 2010 and May 2013 for patients treated by Mini-PNL or standard-PNL through 18 and 30 Fr tracts, respectively, using pneumatic lithotripsy. Semirigid ureteroscope (8.5/11.5 Fr) was used for Mini-PNL and 24 Fr nephroscope for standard-PNL. Both groups were compared in stone free rate(SFR), complications and operative time using Student-t, Mann-Whitney, Chi square or Fisher's exact tests as appropriate in addition to logistic regression analysis. P < 0.05 was considered statistically significant. Mini-PNL (378) and standard-PNL (151) were nearly comparable in patients and stones criteria including stone burden (3.77 ± 2.21 vs 3.77 ± 2.43 cm2; respectively). There was no significant difference in number of tracts or supracostal puncture. Mini-PNL had longer operative time (68.6 ± 29.09 vs 60.49 ± 11.38 min; p = 0.434), significantly shorter hospital stay (2.43 ± 1.46 vs 4.29 ± 1.28 days) and significantly higher rate of tubeless PNL (75.1 vs 4.6%). Complications were significantly higher in standard-PNL (7.9 vs 20.5%; p < 0.001). SFR was significantly lower in Mini-PNL (89.9 vs 96%; p = 0.022). This significant difference was found with multiple stones and large stone burden (> 2 cm2), but the SFR was comparable between both groups with single stone or stone burden ≤ 2 cm. Logistic regression analysis confirmed significantly higher complications and SFR with standard-PNL but with significantly shorter operative time. Mini-PNL has significantly lower SFR when compared to standard-PNL (but clinically comparable) with markedly reduced complications and hospital stay. Most of cases can be performed tubeless. The significant difference in SFR was found with multiple stones or large stone burden (> 2 cm2), but not with single stones or stone burden ≤ 2 cm2.


Context-dependent requirement of G protein coupling for Latrophilin-2 in target selection of hippocampal axons.
The formation of neural circuits requires extensive interactions of cell-surface proteins to guide axons to their correct target neurons. Trans-cellular interactions of the adhesion G protein-coupled receptor latrophilin-2 (Lphn2) with its partner teneurin-3 instruct the precise assembly of hippocampal networks by reciprocal repulsion. Lphn2 acts as a repulsive receptor in distal CA1 neurons to direct their axons to the proximal subiculum, and as a repulsive ligand in the proximal subiculum to direct proximal CA1 axons to the distal subiculum. It remains unclear if Lphn2-mediated intracellular signaling is required for its role in either context. Here, we show that Lphn2 couples to Gα12/13 in heterologous cells; this coupling is increased by constitutive exposure of the tethered agonist. Specific mutations of Lphn2's tethered agonist region disrupt its G protein coupling and autoproteolytic cleavage, whereas mutating the autoproteolytic cleavage site alone prevents cleavage but preserves a functional tethered agonist. Using an in vivo misexpression assay, we demonstrate that wild-type Lphn2 misdirects proximal CA1 axons to the proximal subiculum and that Lphn2 tethered agonist activity is required for its role as a repulsive receptor in axons. By contrast, neither tethered agonist activity nor autoproteolysis were necessary for Lphn2's role as a repulsive ligand in the subiculum target neurons. Thus, tethered agonist activity is required for Lphn2-mediated neural circuit assembly in a context-dependent manner.


Women's management of menstrual symptoms: findings from a postal survey and qualitative interviews.
This paper draws on postal questionnaire and qualitative interview data to investigate women's experiences of and responses to menstrual symptoms. Respondents were drawn from general practices in the Lothian region of Scotland. They described a range of strategies to manage menstrual symptoms, learnt both from personal experience and discussions with others. While most women had spoken to others about periods, this more often related to matters such as changes with age, or pain management, whereas heaviness of blood loss was not usually a subject for discussion. When asked about formal help-seeking women described it as a step reluctantly taken, only if attempts to self manage failed, and that often it was opportunistic, occurring when consulting for something else. It was apparent that women thought of menstrual symptoms, even when felt to be problematic, as 'part and parcel' of female life and not a legitimate reason for adopting illness behaviour. The way that women spoke of managing symptoms suggested that responding to menstrual symptoms takes place within a moral framework and that the only 'legitimate' or 'virtuous' response was a stoical one. Our findings suggest that women with debilitating menstrual symptoms may not have access to the best information, advice or treatments for this. A supported self care approach could help, combining access to high quality information about what is usual and unusual for women, with information about what can help, what treatments are available from which sources and guidance on when and how to seek professional advice. If available in a range of formats, such as features in women's magazines, health-related web-sites and information leaflets, such an approach may help women self-manage their debilitating symptoms even better.


Structure and regulation of desmosomes in intercalated discs: Lessons from epithelia.
For electromechanical coupling of cardiomyocytes, intercalated discs (ICDs) are pivotal as highly specialized intercellular contact areas. ICD consists of adhesive contacts, such as desmosomes and adherens junctions (AJs) that are partially intermingled and thereby form an area composita to provide mechanical strength, as well as gap junctions (GJ) and sodium channels for excitation propagation. In contrast, in epithelia, mixed junctions with features of desmosomes and AJs are regarded as transitory primarily during the formation of desmosomes. The anatomy of desmosomes is defined by a typical ultrastructure with dense intracellular plaques anchoring the cadherin-type adhesion molecules to the intermediate filament cytoskeleton. Desmosomal diseases characterized by impaired adhesive and signalling functions of desmosomal contacts lead to arrhythmogenic cardiomyopathy when affecting cardiomyocytes and cause pemphigus when manifesting in keratinocytes or present as cardiocutaneous syndromes when both cell types are targeted by the disease, which underscores the high biomedical relevance of these cell contacts. Therefore, comparative analyses regarding the structure and regulation of desmosomal contacts in cardiomyocytes and epithelial cells are helpful to better understand disease pathogenesis. In this brief review, we describe the structural properties of ICD compared to epithelial desmosomes and suggest that mechanisms regulating adhesion may at least in part be comparable. Also, we discuss whether phenomena such as hyperadhesion or the bidirectional regulation of desmosomes to serve as signalling hubs in epithelial cells may also be relevant for ICD.


Potentiation of sural nerve Abeta action potential after neurogenic inflammation.
Inflammatory mediators modulate voltage-gated sodium channels through protein kinase-mediated pathways. However, it is not clear whether neurogenic inflammation may also alter the properties of distantly located channels along axon shafts supplying the inflamed dermatome. In this study, localized inflammation was induced via intradermal injection of capsaicin within the receptive field of the sural nerve, and compound action potentials (CAP) evoked by sural nerve stimulation were recorded from the sciatic nerve proximally. The area measured under the A beta CAP increased significantly within 5 min after capsaicin injection. Distal injection of lidocaine at the ankle division of the sural nerve prior to capsaicin injection reversed this increase. In addition, application of a lipophilic protein kinase inhibitor H7 (100 microM) through a perfusion chamber placed on the sciatic nerve also reversed this increase. Our results suggest that during neurogenic inflammation, action potential activity is increased, triggering activation of protein kinases that may rapidly alter membrane conductance to potentiate action potential propagation along peripheral nerves.


Research trends in equine movement analysis, future opportunities and potential barriers in the digital age: A scoping review from 1978 to 2018.
Since Muybridge's 'horse in motion', researchers in the equine movement analysis field continue to improve objective analysis and performance monitoring while ensuring representative data capture. However, subjective evaluation remains the primary method of equine gait analysis in the applied setting, despite evidence highlighting the unreliability of this approach. To map research trends, limitations and opportunities across the diverse equine gait analysis literature. Joanna Briggs Institute and Cochrane systematic scoping review. Search terms were chosen based on the 'PICO' framework and included keywords such as: Equine, Gait, Kinematics and Analysis. Studies were excluded based on predetermined criteria by two independent researchers. Data were extracted from 510 articles from 1978 to 2018. Insights derived from movement analysis appear to be driven by tool availability. Observational research (42.9%) was the most popular study design. Use of wearable technology as a primary research tool is established within the field, accounting for 13.5% of studies. Analysis of limitations identified 17.8% of studies citing challenges to the transferability of research results. Restricted sample size appears to be an underlying contributor to many of the limitations identified. In terms of research opportunities, advances in intervention studies were called for (10.4% of studies) in the following three areas; clinical, rehabilitative exercise and performance/training. This review was confined to research in the English language. Standardised research reporting may alleviate sample size issues by facilitating data pooling, database creation and meta-analyses. Large holistic data collections and application frameworks based on wearable technologies are not reflected in the current equine gait analysis literature and thus represent an interesting opportunity for this field. Progress and lessons learned from the human field of movement analysis can be useful in supporting this potential development.


Comparison of two risk stratification models in elective coronary artery bypass patients.
To compare the Cleveland Clinical Score and EuroSCORE when evaluating patients submitted to elective CABGS in Rio Grande do Sul, RS, Brazil. METHODS; This was a cohort study of 202 patients given CABGS between January 2006 and March 2007. Surgical risk was categorized according to the Cleveland Clinic Score and the EuroSCORE as low, medium or high. The incidence of deaths was measured over a 60-day period. The mean age of patients was 62 ± 10 years and 134 (66%) of them were men. A correlation was observed between the scores for classifying patients into different levels of risk. According to the Cleveland Clinic score and the EuroSCORE, respectively, patients were categorized as follows: 142(70.3%) and 155(76.7%) low risk patients, 56(27.7%) and 43(21.3) intermediate risk patients and 4(2%) and 4(2%) high risk patients; with a Kaplan correlation coefficient of 0.432; p0.001. Thirteen (13, 6.4%) patients died during the first 60 days after surgery. There was a correlation between greater incidence of death and higher risk categories for both the Cleveland Clinic score and the EuroSCORE. Deaths occurred in the Cleveland and EuroSCORE risk groups, respectively, as follows: 6 (4.4%) and 7 (4.5%) in the low risk group; 5 (8.9%) and 5 (11.6%) in the intermediate risk group and 2 (50%) 3 1(25%) in the high risk group. Observed sensitivity for surgical mortality prediction was 72.5% and 66.5% for the Cleveland score and EuroSCORE respectively. The Cleveland Clinic and EuroSCORE surgical risk prediction instruments are both moderately effective for predicting mortality among elective CABGS patients.


Effectiveness of conjunctival bleb scarring by knock-down of heat shock protein 47 in rat model.
To evaluate the effectiveness of knock-down of heat shock protein 47 (HSP47) on conjunctival bleb scarring in a rat model and its possible mechanism. Male Sprague-Dawley rats were used for glaucoma filtration surgery (GFS) and were treated with either phosphate buffered solution, shControl, mitomycin C, or sh-HSP47 using a microsyringe immediately after GFS. The morphology of filtering blebs was observed postoperatively. The levels of HSP47 were analyzed at 2, 5, 8, and 11d after GFS via real-time quantitative polymerase chain reaction (PCR) and Western blot. The silencing effect of HSP47, the expression of collagen I and III, and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS. The protein levels of transforming growth factor-β1 (TGF-β1), phospho-Smad2 (pSmad2), phospho-Smad3 (p-Smad3), and phospho-p38 (p-p38) were also analyzed using Western blot. Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention. The levels of HSP47 were increased significantly at 5, 8, and 11d postoperatively compared to the control group (P<0.05, P<0.01, and P<0.001). The levels of HSP47 protein at day 11 postoperatively were significantly down-regulated after HSP47 silencing using sh-HSP47 adenovirus transfection (P<0.01). Expression levels of collagen I and III within the blebs were significantly reduced in the absence of HSP47 (P<0.01). Moreover, the protein levels of TGF-β1, p-Smad2/3, and p-p38 were dramatically inhibited after treatment with sh-HSP47 (P<0.01). The inhibitory effects of HSP47 knock-down on scarring after GFS have the potential to be an efficacious therapeutic option for the treatment of conjunctival bleb scarring.


Vascular dysfunction induced by elevated glucose levels in rats is mediated by vascular endothelial growth factor.
The purpose of these experiments was to investigate a potential role for vascular endothelial growth factor (VEGF) in mediating vascular dysfunction induced by increased glucose flux via the sorbitol pathway. Skin chambers were mounted on the backs of Sprague-Dawley rats and 1 wk later, granulation tissue in the chamber was exposed twice daily for 7 d to 5 mM glucose, 30 mM glucose, or 1 mM sorbitol in the presence and absence of neutralizing VEGF antibodies. Albumin permeation and blood flow were increased two- to three-fold by 30 mM glucose and 1 mM sorbitol; these increases were prevented by coadministration of neutralizing VEGF antibodies. Blood flow and albumin permeation were increased approximately 2.5-fold 1 h after topical application of recombinant human VEGF and these effects were prevented by nitric oxide synthase (NOS) inhibitors (aminoguanidine and N(G)-monomethyl L-arginine). Topical application of a superoxide generating system increased albumin permeation and blood flow and these changes were markedly attenuated by VEGF antibody and NOS inhibitors. Application of sodium nitroprusside for 7 d or the single application of a calcium ionophore, A23187, mimicked effects of glucose, sorbitol, and VEGF on vascular dysfunction and the ionophore effect was prevented by coadministration of aminoguanidine. These observations suggest a potentially important role for VEGF in mediating vascular dysfunction induced by "hypoxia-like" cytosolic metabolic imbalances (reductive stress, increased superoxide, and nitric oxide production) linked to increased flux of glucose via the sorbitol pathway.


The Influence of Personal Well-Being on Learning Achievement in University Students Over Time: Mediating or Moderating Effects of Internal and External University Engagement.
The current study examined the relationship between students' personal well-being and their learning achievement during university study, and whether such relationship would be mediated or moderated by university engagement. A total of 434 university students from one public university in Hong Kong participated in the study. The participants completed an online survey consisting of personal well-being (cognitive behavioral competence and general positive youth development), university engagement, and learning achievement measures (personal growth, and accumulated GPA as academic achievement) at four time points with a 1-year interval. Results showed that personal well-being measured at the beginning of university study positively predicted students' personal growth and academic achievement after 3 years' study. While the internal dimensions of university engagement (academic challenge and learning with peers) showed longitudinal significant mediational effect, the external dimensions (experience with faculty and campus environment) did not have significant longitudinal moderating effect. Nevertheless, external dimensions of student engagement also showed direct effect on personal growth and academic achievement. The long-standing positive effects of personal well-being on university engagement and subsequently, learning achievement during university years call for more attention to the promotion of holistic development among university students in Hong Kong.


Modelling mass transfer and agitator performance in multiturbine fermentors.
A methodology for mathematically analyzing agitator performance and mass transfer in large multiturbine production fermentors is presented. The application of this approach provides a method for determining axial dissolved oxygen profiles under conditions of known mass transfer rates as a function of agitation-aeration characteristics. A stagewise approach is used which divides the fermentor into a series of mixing cells. This allows for each turbine and mixing cell to be individually optimized. The model also permits the determination of the mass transfer coefficient for each turbine based upon limited dissolved oxygen data. The primary limitation of this approach rests in the limited data and correlations available for multiturbine systems. The structure of the modelling approach can serve as a basis for testing single turbine correlations and adapting them to multiturbine systems. The step-by-step details of the mathematical analysis are presented and interpreted. A series of computer simulations demonstrate the effect of typical fermentor operating variables on the axial dissolved oxygen profile. Further simulations demonstrate the effect of modifying agitator blade numbers on the dissolved oxygen profile and agitator power requirement.


Potentiation of aminoglycoside-induced neuromuscular blockade by protons in vitro and in vivo.
pH-dependent effects of 100 microM streptomycin and various aminoglycosides were examined at frog (Rana pipiens pipiens) sciatic sartorii in vitro by using the intracellular microelectrode recording technique. pH-dependent effects of streptomycin were also examined on indirectly elicited (nerve-stimulated) and directly elicited sartorius muscle twitches in vitro. Furthermore, in vivo effects of systemic pH alterations on neomycin-induced mortality were examined in Sprague-Dawley rats. There was a direct correlation between aminoglycoside potency and the number of basic groups per drug molecule (r = 0.95). At pH 7.2 and 9.0, the effect of pH on aminoglycoside potency correlated inversely with the pKa of the aminoglycoside (r = -0.98). At 0.7 and 2.2 pH units below 7.2, however, aminoglycoside-induced inhibitions of quantal content, end-plate potential amplitude and the indirectly elicited muscle twitch were potentiated by a pH-dependent mechanism that was independent of the pKa of the aminoglycoside. At these pH values, qualitatively similar drug effects were not observed on miniature end-plate potential amplitude and frequency or the directly elicited muscle twitch. Potentiation of aminoglycoside action was observed on mortality of rats, however, when the pH was 0.1 pH unit below 7.4. Thus, potentiation of aminoglycoside-induced neuromuscular blockade by protons in vitro and in vivo was demonstrated and appears to involve the pH-dependent activity of a prejunctional membrane component that regulates voltage-dependent, Ca++-mediated transmitter release.


Spectroscopic properties of Er(3+)/Yb(3+) co-doped Bi(2)O(3)-B(2)O(3)-GeO(2) glasses.
Er(3+)/Yb(3+) co-doped 60Bi(2)O(3)-(40 - x)B(2)O(3)-xGeO(2) (BBG; x=0, 5, 10, 15 mol%) glasses that are suitable for fiber lasers, amplifiers have been fabricated and characterized. The absorption spectra, emission spectra, and lifetime of the (4)I(13/2) level and quantum efficiency of Er(3+):(4)I(13/2) --> (4)I(15/2) transition were measured and calculated. With the substitution of GeO(2) for B(2)O(3), both Delta lambda(eff) and sigma(e) decrease from 75 to 71 nm and 9.88 to 8.12 x 10(-21) cm(2), respectively. The measured lifetime of the (4)I(13/2) level and quantum efficiency of Er(3+):(4)I(13/2) --> (4)I(15/2) transition increase from 1.18 to 1.5 ms and 36.2% to 43.2%, respectively. The emission spectra of Er(3+):(4)I(13/2) --> (4)I(15/2) transition was also analyzed using a peak-fit routine, and an equivalent four-level system was proposed to estimate the stark splitting for the (4)I(15/2) and (4)I(13/2) levels of Er(3+) in the BBG glasses. The results indicate that the (4)I(13/2) --> (4)I(15/2) emission of Er(3+) can be exhibit a considerable broadening due to a significant enhance the peak A, and D emission.


In vitro production of the factors effective in the transfer of experimental autoimmune aspermatogenesis.
We studied the biological effects of the factors released into the culture medium by the lymphocytes from animals sensitized with testicular antigen. The supernatants from cultures of these lymphocytes were active in vitro in the migration inhibition tests because they transferred the sensitivity to normal spleen cells. In vivo, they transferred aspermatogenesis in the allogeneic and xenogeneic system. The results suggest a specific effect on the behaviour of macrophages rather than a direct cytotoxic effect of the active factors.


Efficacy of novel antibody-based drugs against rhinovirus infection: In vitro and in vivo results.
Rhinoviruses (RVs) cause the common cold and are associated with exacerbations of chronic inflammatory respiratory diseases, especially asthma and chronic obstructive pulmonary disease (COPD). We have assessed the antiviral drugs Anaferon for Children (AC) and Ergoferon (containing AC as one of the active pharmaceutical ingredients) in in vitro and in vivo experimental models, in order to evaluate their anti-rhinoviral and immunomodulatory potential. HeLa cells were pretreated with AC, and levels of the interferon-stimulated gene (ISG), 2'-5'-oligoadenylate synthetase 1 (OAS1-A) and viral replication were analyzed. In a mouse model of RV-induced exacerbation of allergic airway inflammation we administered Ergoferon and analyzed its effect on type I (IFN-β), type II (IFN-γ) and type III (IFN-λ) IFNs induction, cell counts in bronchoalveolar lavage (BAL), cytokine (interleukin (IL)-4; IL-6) and chemokine (CXCL10/IP-10; CXCL1/KC) levels. It was shown that AC increased OAS1-А production and significantly decreased viral replication in vitro. Increased IFNs expression together with reduced neutrophils/lymphocytes recruitment and correlated IL-4/IL-6 declination was demonstrated for Ergoferon in vivo. However, there was no effect on examined chemokines. We conclude that AC and Ergoferon possess effects against RV infection and may have potential as novel therapies against RV-induced exacerbations of asthma.


Human error in motorcycle crashes: A methodology based on in-depth data to identify the skills needed and support training interventions for safe riding.
Human error by either rider or other vehicle driver is the primary contributing factor in crashes involving powered-two-wheelers. A human-factor-based crash analysis methodology is key to enhancing the road safety effectiveness of rider training interventions. Our aim is to define a methodology that uses in-depth data to identify the skills needed by riders in the highest risk crash configurations to reduce casualty rates. The methodology is illustrated through a case study using in-depth data of 803 powered-two-wheeler crashes. Seven types of high-risk crash configuration based on pre-crash trajectories of the road-users involved were considered to investigate the human errors as crash contributors. Primary crash contributing factor, evasive maneuvers performed, horizontal roadway alignment and speed-related factors were identified, along with the most frequent crash configurations and those with the greatest risk of severe injury. Straight Crossing Path/Lateral Direction was the most frequent crash configuration and Turn Across Path/Opposing Direction was identified as that with the highest risk of serious injury. Multi-vehicle crashes cannot be considered as a homogenous category of crashes to which the same human failure is attributed, as different interactions between motorcyclists and other road users are associated with both different types of human error and different rider reactions. Human error in multiple-vehicle crashes differed between those configurations related to crossroads and those related to rear-end and head-end crashes. Both single-vehicle crashes and multi-vehicle head-on crashes frequently occur along curves. The involved collision avoidance maneuvers of the riders differed significantly among the highest risk crash configurations. The most relevant lack of skills are identified and linked to their most representative context. In most cases a combination of different skills was required simultaneously to avoid the crash. The results contribute to understand the motorcyclists' responses in high-risk crash scenarios. The findings underline the need to group accident cases, beyond the usual single-vehicle versus multi-vehicle collision approach. The different interactions with other road users should be considered to identify the competencies of the motorcyclists needed to reduce crash risks. Our methodology can be applied to increase the motorcyclists' safety by supporting preventive actions based on riders' training and eventually ADAS design.


Scintiphotography in diagnosis of urinary fistula after renal transplantation.
Scintiphotographic studies in six patients with ureteral fistula following renal transplantation are presented. Images were obtained using 99m-Tc-Sn-DTPA or 131-I-orthoiodohippurate. Urinary leakage was accurately detected in each case but the pattern of extravasation is highly variable. When carefully performed, radionuclide scintiphotography is a safe and effective method for detecting urinary leakage after renal transplantation.


Managing delirium and agitation in elderly hospitalized orthopaedic patients: Part 2--Interventions.
Delirium, a disorder of consciousness that may afflict over one-half of elderly surgical orthopaedic patients is a common sequela of surgery in the elderly. Agitation, either as an element of the delirium or dimension of a preexisting dementia, is another common behavioral problem that can confront the orthopaedic nurse in acute care. It is time now to tear down the barriers to intelligent and compassionate care of patients with agitation and delirium, including late or missed recognition and diagnosis, biases about what is "normal" and acceptable behavior in the elderly, and lack of familiarity with pharmacologic strategies. In Part 1 (Jan/Feb issue), current thinking about the phenomena was presented, including hypotheses about causation and pathophysiology. That foundation is intended to serve as the basis for the current discussion. The triad of interventions available to manage disorganized behavior in elderly orthopaedic patients is presented in Part 2. They include an extensive selection of pharmacologic options, a discussion of therapeutic use of self and environmental-organizational issues to address and consider on a case-by-case basis. Though it may be impossible to prevent behavioral decompensation during an acute orthopaedic admission, it is certainly possible to improve our performance to date, using a compassionate, intelligent, and inclusive approach with every patient.


Translations of the Practice Environment Scale of the Nursing Work Index: A systematic review.
Since 2002, the Practice Environment Scale of the Nursing Work Index has been used worldwide to evaluate nurse work environments. High quality translations in different languages can help advance science and inform practice globally. The study purposes were to conduct a systematic review of published translations of the instrument and to assess their linguistic equivalence and psychometric performance. We conducted a comprehensive search, a quality assessment and synthesis of linguistic equivalence, reliability, and validity data. Studies published through July 2021 were identified in the CINAHL, LILACS, EMCare, and Scopus databases. Thirty-eight publications were selected, comprising 46 translations into 24 languages and 15 language variants, and 35 countries. Translations are in predominantly European, Southeast Asian, and Middle Eastern languages. Two-thirds of the translations reflected medium to high fulfillment of translation quality criteria. The GRADE ratings, reflecting satisfactory fulfillment of cross-cultural equivalence and psychometric properties, were predominantly high (n = 23), then low (n = 15), then moderate (n = 8). The identified translations will support the advancement of global science and the improvement of nurses' work environments.


Pharmacokinetics of elemental platinum (ultrafiltrate and total) after a thirty minute intravenous infusion of ormaplatin.
Preclinical data suggest that ormaplatin (tetrachloro-(dl-trans)-1, 2-diamminocyclohexaneplatinum) has substantial activity in cisplatin-resistant tumor models and may be less nephrotoxic than cisplatin. Based on these data we initiated a phase I clinical trial in patients with refractory metastatic cancer. This report characterizes the pharmacokinetic profile of both the total plasma concentrations of elemental platinum and the unbound ultrafiltrate concentrations of elemental platinum, following a 30 min intravenous infusion of ormaplatin. Platinum concentrations were determined by AAS, and pharmacokinetic parameters for both the total plasma concentration and the ultrafiltrate concentration of elemental platinum were determined using both compartmental and noncompartmental methods. Twenty-eight patients (14 males and 14 females; median age, 58) received ormaplatin. There was a linear relationship between Cmax and dose (r2 = 0.945) and AUC and dose (r2 = 0.976). Ormaplatin is more accurately described by a two-compartment model than by a one-compartment model. The distribution half-life (t1/2 alpha) was 0.3 h and the terminal half-life (t1/2 beta) was 39.1 h. The volume of the central compartment (V) was 68.6 L and the volume of distribution at steady state (Vdss) was 183 L. Like total plasma platinum, unbound platinum is also best characterized by a two-compartment model. The elimination of free platinum is also biphasic with a distribution half-life (t1/2 alpha) of 0.3 h and a terminal half-life (t1/2 beta) of 19.3 h. The mean volume of the central compartment (V) was 200.5 L, and the mean volume of distribution at steady state (Vdss) was 560.5 L. Clinical development of ormaplatin has been terminated due to increased frequency of neurological complications noted over other platinum agents; however, the pharmacokinetics are, in general, similar to those of other clinically used platinum compounds.


Neuroendocrine neoplasms and somatostatin receptor subtypes expression.
Neuroendocrine neoplasms (NENs) show wide spectrum of clinical course - from benign biological potential to recurrences and rapidly progressive disease. Somatostatin analogs that bind to somatostatin receptor are part of the therapy; detection and evaluation of activation of somatostatin receptor subtypes are part of the process of new therapy induction. When using RT-PCR method and immunohistochemistry, it is possible to detect more than two SSTR subtypes in majority or all neuroendo-crine neoplasms regardless tumor origin. Generally with some exceptions, from the viewpoint of tumor grade - apart the site of origin, there is a tendency to decrease the percentage of SSTRs expression; 100% (G1, 2)-85.7% (G3) for SSTR 1; 81.8% (G1, 2)-61.9% (G3) for SSTR 2; 54.5% (G1, 2)-52.4% (G3) for SSTR 3; 9% (G1, 2)-4.8% (G3) for SSTR 5. Different studies indi-cate significant differences in the expression of SSTR 1 and 2A and 2B between NEC G3 small cell type and non-small cell type. Further research on SSTRs expression in NEN could serve as base to development and improvement of somatostatin analogs' pharmacotherapy in patients with unsatisfactory course.


Psychiatric symptoms, risky behavior, and HIV infection.
These data are internally consistent and lead to several conclusions, as follows: Elevated levels of psychiatric symptoms were found among IDUs in methadone treatment as compared to their counterparts who were out of treatment. IVDUs who entered treatment had higher symptom levels than those who did not enter treatment. Higher symptom levels were found among injectors than noninjectors, and needle sharers had especially high psychiatric symptom levels. Higher symptom levels were found among those who seroconverted in the 6 months following notification, but not thereafter. Symptom levels did not distinguish between HIV-positive and HIV-negative individuals 24 months following notification of seropositivity. Taken together, these findings indicate that elevated psychiatric symptoms are risk factors for continued high risk behavior, as well as for seroconversion. The data add to those of Brooner and colleagues (1993), who demonstrated that ASPD serves as a risk factor for HIV infection. The fact that antisocial personality disorder and psychiatric severity are associated with risky behavior and with actual HIV infection further expands earlier findings showing that these two factors are associated with poorer treatment outcome. Other axis II disorders (e.g., borderline or narcissistic), as well as other axis I disorders with high symptom levels that were not well represented in these studies (schizophrenia, manic depressive illness), may also show similar elevated rates of risky behavior and seroconversion, although there is a scarcity of data currently available to assess the risk behavior of these patients. The evidence from treatment studies that psychiatrically focused therapies, when combined with substance abuse treatment, can improve overall outcome for patients with clinically significant levels of psychiatric symptoms may be relevant in the design of future risk reduction efforts. That is, these treatment outcome studies may serve as a starting point for exploring the feasibility and efficacy of using psychiatrically focused treatment to reduce risky behavior and HIV infection among psychiatrically symptomatic IDUs.


Effect of co-culture with theca interna on nuclear maturation of horse oocytes with low meiotic competence, and subsequent fusion and activation rates after nuclear transfer.
We conducted this study to examine whether or not co-culture with theca cells improves the maturation rate of horse oocytes with compact cumuli and to evaluate the cytoplasmic competence of oocytes after maturation by assessing fusion, activation and cleavage rates after nuclear transfer. We collected oocytes by scraping follicles from slaughterhouse-derived ovaries and classified them as having an expanded or a compact cumulus. Expanded oocytes were matured in M199 supplemented with 10% FBS and 5 microU/ml FSH for 24 h: compact oocytes were cultured in the same medium, or they were co-cultured in the same medium with theca interna explants, for 24 or 42 h. Oocytes were held with or without 10 microg/ml cytochalasin B, before washing and micromanipulation. and they were fused with donor fibroblasts by electrical pulse. Fused oocytes were activated with Ca ionophore/cycloheximide, cultured for 5 days, and stained with Hoechst to assess nuclear development. We considered oocytes with an enlarged nucleus, or having cleavage with multiple nuclei, to be activated. There was no significant difference in overall maturation rate between compact oocytes cultured with theca and compact controls. When these two groups were combined, there was a significant increase in the proportion of oocytes in MII between 24 and 42 h (P < 0.05). Expanded oocytes had a significantly higher rate of maturation than did compact oocytes (64% versus 25-30%; P < 0.001). There were no significant differences in rates of successful enucleation, fusion, activation or cleavage between compact control and compact + theca oocytes, nor between compact and expanded oocytes; however, expanded oocytes treated with cytochalasin B had a significantly higher survival rate after enucleation than did untreated expanded oocytes (P < 0.05). Three embryos developed from recombined oocytes, with maximum cleavage to 10 cells. The results of this study indicate that co-culture with theca cells does not increase either nuclear or cytoplasmic maturation of compact oocytes. Cytochalasin B is helpful in increasing survival of horse oocytes during enucleation. In vitro matured equine oocytes have the potential to develop into embryos after nuclear transfer; this is the first full report of production of cloned embryos in this species.


Basal structure and attachment of flagella in cells of Proteus vulgaris.
Abram, Dinah (Purdue University, Lafayette, Ind.), Henry Koffler, and A. E. Vatter. Basal structure and attachment of flagella in cells of Proteus vulgaris. J. Bacteriol. 90:1337-1354. 1965.-The attachment of flagella to cells of Proteus vulgaris was studied electron microscopically with negatively stained and shadow-cast preparations of ghosts from standard cultures and from special cultures that produced "long forms." The flagellum, the basal portion of which is hooked, arises within the cell from a nearly spherical structure, 110 to 140 A in diameter. This structure appears to be associated with the cytoplasmic membrane; it may be a part of the membrane or a separate entity that lies just beneath the membrane. Flagella associated with cell walls free from cytoplasmic membrane frequently have larger bodies, 200 to 700 A in diameter, associated with their base. These structures probably consist at least partly of fragments of the cytoplasmic membrane, a portion of which folds around a smaller structure. Flagella in various stages of development were observed in long forms of P. vulgaris cells grown at low temperature. The basal structure of these flagella was similar to that of the long or "mature" flagella. Strands connecting the basal structures were observed in ghosts of long forms; these strands appear to be derived from the cytoplasmic membrane. Flagella were found to be attached to fragments of cell wall and to cytoplasmic membrane in a similar manner as they are attached to ghosts. In isolates of flagella that have been separated from the cells mechanically, the organelles often terminate in hooks which almost always appear naked, but have a different fine structure than the flagellum proper.


[Depression therapy for somatic diseases].
A review of works devoted to the problem of psychopharmacotherapy of depression in general medical practice is presented. The issues of its comorbidity with somatic and neurological diseases, as well as multimorbidity are discussed. Both direct and side-effects of antidepressants, which are important for effective therapy of not only affective disorders proper, but also the symptoms of the leading pathology, are considered in detail for individual organs and systems. The analysis of the preferred pharmacological classes of antidepressants, which are drugs of first choice, taking into account the somatic condition of the patient, is carried out, and drugs are indicated, the appointment of which is undesirable for the treatment of a patient with a certain disease. The presented results are aimed both at increasing the efficiency of therapy for patients with general medical level of health care, and at increasing the safety of treatment of psychiatric patients with concomitant somatic disorders.


Molecular effectors in the chronic exposure to arsenic as early and sensitive biomarkers in developing Rhinella arenarum toads.
Arsenic, a natural element of ecological relevance, is one of the most toxic elements present in various regions of the world. It can be found in natural water sources throughout Argentina in concentrations between 0.01 and 15mgL-1. The Argentinean autochthonous toad Rhinella arenarum was selected to study the molecular mechanisms involved in the effects and response to the chronic As exposure along its embryonic and larval development. We evaluated the effects on MAPK signal transduction pathway and transcription factors c-FOS and c-JUN, and the regulation of the expression at protein levels of different antioxidant enzymes. Our results indicated that As is modulating the MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclear fraction along the embryonic development and mainly at the beginning of the larval stage. Through this pathway, As can upregulate transcription factors like c-FOS and c-JUN, impacting the antioxidant response of the exposed embryos and larvae through antioxidant enzymes and recycling of GSH. Arsenic triggered specifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. In particular, the expression levels of SOD, CAT and GST enzymes analyzed by Western blot showed a similar behavior to their enzymatic activities in our previous work. This fact suggests that not only the synthesis of these antioxidant enzymes but also their rapid degradation after inactivation would be regulated in response to ROS levels. Antioxidant enzymes may show dual responses of induction and inactivation followed by degradation depending on the levels of oxidative stress and impact on ROS targets when the exposure is sustained in time and intensity. We also performed a probability of exceedence analysis including our previous results to visualize a progression of the response in time and also established the best early-responding biomarkers at the lowest As concentrations. As a conclusion, the molecular biomarkers such as the MAPKs MEK and ERK and transcription factors c-FOS and c-JUN are early induced in the response of developing toad embryos exposed to very low As concentrations in water. The advantage of counting with molecular biomarkers early responding to low concentrations of As in a chronic exposure is that they may anticipate the irreversible damage at later developmental stages due to the constant oxidative challenge.


Further studies on the susceptibility of raccoons (Procyon lotor) to a rabies virus of skunk origin and comparative susceptibility of striped skunks (Mephitis mephitis).
Two raccoons (Procyon lotor) were inoculated in the masseter muscles with 10(5.9) mouse intracerebral lethal dose50 (MICD50) of a rabies virus isolated from a naturally infected Iowa (USA) striped skunk (Mephitis mephitis). Five striped skunks were inoculated with either 10(0.7) or 10(2.1) MICLD50 of the same isolate. All five skunks died within 35 days following inoculation. Both raccoons survived 273 days without adverse effects, and virus was not isolated from saliva samples taken at between 25 and 273 days following inoculation.


ClpP-deletion impairs the virulence of Legionella pneumophila and the optimal translocation of effector proteins.
The opportunistic bacterial pathogen Legionella pneumophila uses substrate effectors of Dot/Icm type IVB secretion system (T4BSS) to accomplish survival and replication in amoebae cells and mammalian alveolar macrophages. During the conversion between its highly resistant, infectious dormant form and vigorously growing, uninfectious replicative form, L. pneumophila utilizes a complicated regulatory network in which proteolysis may play a significant role. As a highly conserved core protease, ClpP is involved in various cellular processes as well as virulence in bacteria, and has been proved to be required for the expression of transmission traits and cell division of L. pneumophila. The clpP-deficient L. pneumophila strain failed to replicate and was digested in the first 3 h post-infection in mammalian cells J774A.1. Further investigation demonstrates that the clpP deficient mutant strain was unable to escape the endosome-lysosomal pathway in host cells. We also found that the clpP deficient mutant strain still expresses T4BSS components, induces contact-dependent cytotoxicity and translocate effector proteins RalF and LegK2, indicating that its T4BSS was overall functional. Interestingly, we further found that the translocation of several effector proteins is significantly reduced without ClpP. The data indicate that ClpP plays an important role in regulating the virulence and effector translocation of Legionella pneumophila.


The prospects of antimicrobial coated medical implants.
The implants are increasingly being a part of modern medicine in various surgical procedures for functional or cosmetic purposes. The progressive use of implants is associated with increased infectious complications and prevention of such infections always remains precedence in the clinical settings. The preventive approaches include the systemic administration of antimicrobial agents before and after the surgical procedures as well as the local application of antibiotics. The relevant literature and existing clinical practices have highlighted the role of antimicrobial coating approaches in the prevention of implants associated infections, although the applications of these strategies are not yet standardized, and the clinical efficacy is not much clear. The adequate data from the randomized control trials is challenging because of the unavailability of a large sample size although it is compulsory in this context to assess the clinical efficacy of preemptive practices. This review compares the efficacy of preventive approaches and the prospects of antimicrobial-coated implants in preventing implant-related infections.


Low serum vitamin B12 in Alzheimer-type dementia.
Serum vitamin B12 levels (as determined by radio-immunoassay) were measured in 20 subjects aged 65 years and over with Alzheimer-type dementia, 20 age-matched subjects with non-Alzheimer type dementia and 20 age-matched subjects with no dementia. Serum vitamin B12 levels were significantly lower and serum vitamin B12 deficiency was significantly more frequent in subjects with Alzheimer-type dementia and were independent of age, sex, haematological abnormality or serum folate.


Vaccine-induced CD8+ central memory T cells in protection from simian AIDS.
Critical to the development of an effective HIV vaccine is the identification of adaptive immune responses that prevent infection or disease. In this study we demonstrate in a relevant nonhuman primate model of AIDS that the magnitude of vaccine-induced virus-specific CD8(+) central memory T cells (T(CM)), but not that of CD8(+) effector memory T cells, inversely correlates with the level of SIVmac251 replication, suggesting their pivotal role in the control of viral replication. We propose that effective preventive or therapeutic T cell vaccines for HIV-1 should induce long-term protective central memory T cells.


A three-level model for binary time-series data: the effects of air pollution on school absences in the Southern California Children's Health Study.
A three-level model is proposed to simultaneously examine the effects of daily exposure to air pollution and individual risk factors on health outcomes without aggregating over subjects or time. We used a logistic transition model with random effects to take into account heterogeneity and overdispersion of the observations. A distributed lag structure for pollution has been included, assuming that the event on day t for a subject depends on the levels of air pollution for several preceding days. We illustrate this proposed model via detailed analysis of the effect of air pollution on school absenteeism based on data from the Southern California Children's Health Study.


New insights into the fundamental chemical nature of ionic liquid film formation on magnesium alloy surfaces.
Ionic liquids (ILs) based on trihexyltetradecylphosphonium coupled with either diphenylphosphate or bis(trifluoromethanesulfonyl)amide have been shown to react with magnesium alloy surfaces, leading to the formation a surface film that can improve the corrosion resistance of the alloy. The morphology and microstructure of the magnesium surface seems critical in determining the nature of the interphase, with grain boundary phases and intermetallics within the grain, rich in zirconium and zinc, showing almost no interaction with the IL and thereby resulting in a heterogeneous surface film. This has been explained, on the basis of solid-state NMR evidence, as being due to the extremely low reactivity of the native oxide films on the intermetallics (ZrO2 and ZnO) with the IL as compared with the magnesium-rich matrix where a magnesium hydroxide and/or carbonate inorganic surface is likely. Solid-state NMR characterization of the ZE41 alloy surface treated with the IL based on (Tf)2N(-) indicates that this anion reacts to form a metal fluoride rich surface in addition to an organic component. The diphenylphosphate anion also seems to undergo an additional chemical process on the metal surface, indicating that film formation on the metal is not a simple chemical interaction between the components of the IL and the substrate but may involve electrochemical processes.


Marrow transplantation in patients with thalassemia responsive to iron chelation therapy.
Patients with homozygous beta-thalassemia, who have a good prognosis during treatment with conventional therapy, appear to have an especially high probability of hematologic cure with bone marrow transplantation, although the morbidity and mortality associated with such treatment are not established. The records of all patients with thalassemia who received bone marrow transplants from HLA-identical donors in Pesaro, Italy, were examined from October 1982 through May 1992. Detailed evaluation of the outcome was conducted in the 89 patients identified as being in class 1 according to the Pesaro classification, in which hepatomegaly, portal fibrosis, and the inadequacy of iron chelation therapy are considered independent risk factors, and the patients are classified as being in class 1 if none of these factors are present, class 2 if one or two of the factors are present, and class 3 if all three factors are present. Sixty-four of the patients had been prepared for transplantation with a drug regimen in current use that includes busulfan and cyclophosphamide followed by cyclosporine as prophylaxis against acute graft-versus-host disease (protocol 6). There were seven deaths, all within 101 days of transplantation. Two of the 64 patients treated according to protocol 6 died. The probabilities of survival, rejection-free survival, death from causes unrelated to rejection, and rejection were 0.92, 0.85, 0.06, and 0.08, respectively, in the total group and 0.97, 0.93, 0.03, and 0.04 in the 64 patients treated according to protocol 6. Preliminary evidence suggests that there was useful unloading of tissue iron deposits. The high probability of cure with little early or late morbidity and mortality suggests that patients with class 1 thalassemia who have HLA-identical donors available should be treated by bone marrow transplantation. However, this was not a controlled trial, so we cannot directly compare the outcome with that of conventional treatment.


Photoacoustic imaging of angiogenesis in a subcutaneous islet transplant site in a murine model.
Islet transplantation (IT) is an established clinical therapy for select patients with type-1 diabetes. Clinically, the hepatic portal vein serves as the site for IT. Despite numerous advances in clinical IT, limitations remain, including early islet cell loss posttransplant, procedural complications, and the inability to effectively monitor islet grafts. Hence, alternative sites for IT are currently being explored, with the subcutaneous space as one potential option. When left unmodified, the subcutaneous space routinely fails to promote successful islet engraftment. However, when employing the previously developed subcutaneous "deviceless" technique, a favorable microenvironment for islet survival and function is established. In this technique, an angiocatheter was temporarily implanted subcutaneously, which facilitated angiogenesis to promote subsequent islet engraftment. This technique has been employed in preclinical animal models, providing a sufficient means to develop techniques to monitor functional aspects of the graft such as angiogenesis. Here, we utilize photoacoustic imaging to track angiogenesis during the priming of the subcutaneous site by the implanted catheter at 1 to 4 weeks postcatheter. Quantitative analysis on vessel densities shows gradual growth of vasculature in the implant position. These results demonstrate the ability to track angiogenesis, thus facilitating a means to optimize and assess the pretransplant microenvironment.


Helminth infection and helminth-derived products: A novel therapeutic option for non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is closely related to obesity, diabetes, and metabolic syndrome (MetS), and it has become the most common chronic liver disease. Helminths have co-evolved with humans, inducing multiple immunomodulatory mechanisms to modulate the host's immune system. By using their immunomodulatory ability, helminths and their products exhibit protection against various autoimmune and inflammatory diseases, including obesity, diabetes, and MetS, which are closely associated with NAFLD. Here, we review the pathogenesis of NAFLD from abnormal glycolipid metabolism, inflammation, and gut dysbiosis. Correspondingly, helminths and their products can treat or relieve these NAFLD-related diseases, including obesity, diabetes, and MetS, by promoting glycolipid metabolism homeostasis, regulating inflammation, and restoring the balance of gut microbiota. Considering that a large number of clinical trials have been carried out on helminths and their products for the treatment of inflammatory diseases with promising results, the treatment of NAFLD and obesity-related diseases by helminths is also a novel direction and strategy.


Combined density functional/polarizable continuum model study of magnetochiral birefringence: can theory and experiment be brought to agreement?
The magnetic-field-induced axial birefringence (magnetochirality) of five closed-shell chiral molecules (three substituted oxiranes, carvone, and limonene) is studied at the density functional theory level using Becke's 3-parameter Lee-Yang-Parr functional and frequency-dependent quadratic response theory. The influence of the environment and the conformational distribution on the property is also studied. The environment effects are described by the polarizable continuum model in its integral-equation formulation. The effect of the conformational distribution is investigated by performing calculations on several conformers-for carvone and limonene-followed by Boltzmann averaging. The calculated values for the magnetochiral birefringence are compared to previous ab initio results and experimental data where available. The refined model presented here brings the ab initio values closer to experiment. Still, disagreements remain in some cases and it appears difficult to resolve these discrepancies.


Using Machine Learning to Select Breast Implant Volume.
In breast augmentation surgery, the selection of the appropriate breast implant size is a crucial step that can greatly impact patient satisfaction and the outcome of the procedure. However, this decision is often based on the subjective judgment of the surgeon and the patient, which can lead to suboptimal results. In this study, we aimed to develop a machine-learning approach that can accurately predict the size of breast implants selected for breast augmentation surgery. We collected data on patient demographics, medical history, and surgeon preferences from a sample of 1000 consecutive patients who underwent breast augmentation. This information was used to train and test a supervised machine learning model to predict the size of breast implants. Our study demonstrated the effectiveness of the algorithm in predicting breast implant size, achieving a Pearson's correlation coefficient of 0.9335 (p <0.001). The model generated accurate predictions in 86% of the instances, with a Mean Absolute Error (MAE) of 27.10 ml. Its effectiveness was confirmed in the reoperation group, in which 36 of 57 (63%) patients would have received a more suitable implant size if the model's suggestion were followed, potentially avoiding reoperation. Our findings show that machine learning can accurately predict the chosen size of breast implants in augmentation surgery. By integrating our AI model into a decision support system for breast augmentation surgery, essential guidance can be provided to both the surgeons and patients. This not only streamlines the implant selection process but also facilitates enhanced communication and decision-making, ultimately leading to more reliable outcomes and improved patient satisfaction.


Dynamic quantitative detection of ABC transporter family promoter methylation by MS-HRM for predicting MDR in pancreatic cancer.
The main focus of the present study was to evaluate whether ABC transporter family promoter methylation predicted multidrug resistance in gemcitabine-resistant cancer cell lines (BxPC-3/Gem and PANC-1/Gem). Using low concentrations of gemcitabine, the cell lines acquired drug resistance with different initial gemcitabine concentrations. A novel technology, methylation-sensitive high-resolution melting, was used to monitor the dynamic changes of ABC transporter family promoter methylation, including ATP binding cassette subfamily B member 1 (ABCB1), ATP binding cassette subfamily C (ABCC) and ATP binding cassette subfamily G member 2 (ABCG2) mRNA expression. It was revealed that, with elevation of initial gemcitabine concentration, expression of ABCB1, ABCC and ABCG2 mRNA and corresponding downstream proteins was increased while promoter methylation was decreased. These discoveries indicate that promoter methylation of ABCB1, ABCC and ABCG2 may be a valuable indicator of drug-resistance characteristics in BxPC-3/Gem and PANC-1/Gem cells via quantitative and simultaneous detection. These results also implied that MDR in pancreatic cancer not only arises from gene mutation, but also originates from promoter methylation.


Dynamic correlations with time-dependent quantum Monte Carlo.
In this paper, we solve quantum many-body problem by propagating ensembles of trajectories and guiding waves in physical space. We introduce the "effective potential" correction within the recently proposed time-dependent quantum Monte Carlo methodology to incorporate the nonlocal quantum correlation effects between the electrons. The associated correlation length is calculated by adaptive kernel density estimation over the walker distribution. The general formalism is developed and tested on one-dimensional helium atom in laser field of different intensities and carrier frequencies. Good agreement with exact results for the atomic ionization is obtained.


Pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer.
Overexpression of HER2 - found in approximately 15-20% of all breast cancers - is a negative prognostic factor. Although trastuzumab significantly improves the prognosis of HER2-positive breast cancer, half of the patients with metastatic breast cancer experience disease progression within 1 year. Pertuzumab is a novel HER2-targeted humanized monoclonal antibody that binds to the dimerization domain of HER2 and acts synergically with trastuzumab in inhibiting tumor progression. The CLEOPATRA trial demonstrated that adding pertuzumab to trastuzumab plus docetaxel significantly prolonged progression-free survival and overall survival without increasing severe adverse events. Conclusively, pertuzumab was approved by the US FDA in June 2012 for use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer. Furthermore, various clinical trials to evaluate the efficacy and safety of pertuzumab combined with other cytotoxic agents are ongoing at present. Thus, pertuzumab has been becoming important for the treatment of patients with HER2-positive metastatic breast cancer.


Tuberculosis after liver transplantation in a large center in New York City: QuantiFERON® -TB Gold-based pre-transplant screening performance and active tuberculosis post-transplant.
Pre-transplant screening for latent tuberculosis infection (LTBI) is a complex consideration that varies by institution. Inconsistent performance of interferon-gamma release assay (IGRA) further complicates screening. Data regarding LTBI screening outcomes and test characteristics in a large, foreign-born pre-transplant population within the United States are limited. In this retrospective study, patients who received QuantiFERON® -TB Gold (QFT) prior to liver transplantation (LT) were included. Characteristics of patients were compared by QFT result, and predictors of indeterminate results were evaluated. Similar comparisons were performed between patients who developed active TB and those who did not. Of 148 patients screened, the rate of positive, indeterminate, and negative testing was 13.5% (20/148), 27% (40/148), and 59% (88/148), respectively. An indeterminate QFT result was more than 16 times more likely in patients with a Model for End-stage Liver Disease score >25 (odds ratio [OR] 16.7; 95% confidence interval [CI], 2.1-132.0; P = .008) and more than 4 times when performed in our institution's lab compared with commercial lab (OR 4.1; 95% CI, 1.34-12.44; P = .013). The overall TB incidence was 1102/100 000 transplant cases. No patient who developed active TB had a positive QFT. All were born outside of the United States (P = .06) and had pre-transplantation chest imaging demonstrating granulomatous disease (P = .006). Our experience further highlights the challenges of LTBI screening prior to LT and suggests that QFT may be a poor predictor of active TB in higher risk pre-transplant populations. Candidates should be screened as early as possible to optimize QFT performance, and local epidemiological data should be used to create institution-specific screening protocols in areas with large populations from TB-endemic regions. Management should consider TB risk factors, QFT, and imaging instead of reliance on QFT testing alone.


LEDs: Sources and Intrinsically Bandwidth-Limited Detectors.
The increasing demand for light emitting diodes (LEDs) is driven by a number of application categories, including display backlighting, communications, signage, and general illumination. Nowadays, they have also become attractive candidates as new photometric standards. In recent years, LEDs have started to be applied as wavelength-selective photo-detectors as well. Nevertheless, manufacturers' datasheets are limited about LEDs used as sources in terms of degradation with operating time (aging) or shifting of the emission spectrum as a function of the forward current. On the contrary, as far as detection is concerned, information about spectral responsivity of LEDs is missing. We investigated, mainly from a radiometric point of view, more than 50 commercial LEDs of a wide variety of wavelength bands, ranging from ultraviolet (UV) to near infrared (NIR). Originally, the final aim was to find which LEDs could better work together as detector-emitter pairs for the creation of self-calibrating ground-viewing LED radiometers; however, the findings that we are sharing here following, have a general validity that could be exploited in several sensing applications.


Loss of PRDM11 promotes MYC-driven lymphomagenesis.
The PR-domain (PRDM) family of genes encodes transcriptional regulators, several of which are deregulated in cancer. By using a functional screening approach, we sought to identify novel tumor suppressors among the PRDMs. Here we demonstrate oncogenic collaboration between depletion of the previously uncharacterized PR-domain family member Prdm11 and overexpression of MYC. Overexpression of PRDM11 inhibits proliferation and induces apoptosis. Prdm11 knockout mice are viable, and loss of Prdm11 accelerates MYC-driven lymphomagenesis in the Eµ-Myc mouse model. Moreover, we show that patients with PRDM11-deficient diffuse large B-cell lymphomas (DLBCLs) have poorer overall survival and belong to the nongerminal center B-cell-like subtype. Mechanistically, genome-wide mapping of PRDM11 binding sites coupled with transcriptome sequencing in human DLBCL cells evidenced that PRDM11 associates with transcriptional start sites of target genes and regulates important oncogenes such as FOS and JUN. Hence, we characterize PRDM11 as a putative novel tumor suppressor that controls the expression of key oncogenes, and we add new mechanistic insight into B-cell lymphomagenesis.


Impact of curative treatment on the physical fitness of patients with esophageal cancer: A systematic review and meta-analysis.
Esophageal cancer and curative treatment have a significant impact on the physical fitness of patients. Knowledge about the course of physical fitness during neoadjuvant therapy and esophagectomy is helpful to determine the needs for interventions during and after curative treatment. This study aims to review the current evidence on the impact of curative treatment on the physical fitness of patients with esophageal cancer. A systematic literature search of PubMed, Embase, Cinahl and the Cochrane Library was conducted up to March 29, 2021. We included observational studies investigating the change of physical fitness (including exercise capacity, muscle strength, physical activity and activities of daily living) from pre-to post-neoadjuvant therapy and/or from pre-to post-esophagectomy. Quality of the studies was assessed and a meta-analysis was performed using standardized mean differences. Twenty-seven articles were included. After neoadjuvant therapy, physical fitness decreased significantly. In the first three months after surgery, physical fitness was also significantly decreased compared to preoperative values. Subgroup analysis showed a restore in exercise capacity three months after surgery in patients who followed an exercise program. Six months after surgery, there was limited evidence that exercise capacity restored to preoperative values. Curative treatment seems to result in a decrease of physical fitness in patients with esophageal cancer, up to three months postoperatively. Six months postoperatively, results were conflicting. In patients who followed a pre- or postoperative exercise program, the postoperative impact of curative treatment seems to be less.


Ambulatory blood pressure monitoring in the design of studies on antihypertensive drug efficacy.
Ambulatory blood pressure monitoring (ABPM) provides advantages for studies of the efficacy of antihypertensive drugs in addition to demonstrating antihypertensive effects in daily life conditions. For example, ABPM is devoid of the "white coat" effect and can thus more precisely estimate the relative proportion of responders and nonresponders to treatment. It also may reduce the study size because of the greater reproducibility of 24 h average blood pressure (BP) (as compared to clinic BP) and the lack of a substantial placebo effect, which eliminates the need for a placebo group. Some disadvantages exist, including the inability of automatic ABPM to consistently provide accurate BP readings and to estimate BP variability. Finally, hourly average BPs are less reproducible than their average 24 h counterpart, which may make it more difficult to statistically demonstrate an antihypertensive effect throughout the 24 h. Some of these disadvantages, however, may be reduced in the near future by new ABPM devices.


[Permanence of nurses in their profession].
The main cause for nursing shortage in the world is that nurses are withdrawing the profession. However few research has been carried out to prove this. This study investigates nurses' permanence in job and their motives for withdrawing it. Researchers tried to contact 1112 nurses who enrolled the profession after finishing the undergraduate nursing course at the University of São Paulo at Ribeirão Preto College of Nursing, Brazil, in the period from 1957 to 1990. They were not able to contact 95 nurses (8.54%) from the total. Therefore, 1017 (91.46%) were contacted by mail, telephone or interview to answer a questionnaire, 808 (72.66%) answered, 194 (17.45%) did not reply, 4 (0.36%) refused to answer and 11 (0.99%) died, generating the following data: 19 (2.35%) never worked, 661 (81.81%) are working in the profession, 102 (12.62%) worked and withdrew nursing, 26 (3.22%) retired. Considering this group, the analysis showed that the percentage who left the profession is small, nevertheless other studies are suggested in order to enable the comparison of these results. The motives for their permanence are their attachment to the profession, even though they say that their work is not recognized and they are badly paid. The reasons for withdrawing the profession are family and personal problems as well as constant changes in the schedule and general frustration. In sum, nurses love their profession and would like to continue working. Some of them are returning and asking for better conditions.


Solvent-dependent nuclearity, geometry and catalytic activity of [(SPhos)Pd(Ph)Cl]2.
The nuclearity and structures of the palladium complex [(SPhos)Pd(Ph)Cl]2 in the solid and solution states are revisited using a combination of Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy, NMR spectroscopy, mass spectrometry, DFT calculations and trapping experiments. The complex was tested for its catalytic activity in the coupling reaction between chlorobenzene and n-hexylamine, where different deactivation behaviours were observed in toluene, 1,4-dioxane and DMF.


What Does a Single Semen Sample Tell You? Implications for Male Factor Infertility Research.
Semen parameters are variable within individuals, but it is unclear whether 1 semen sample could represent a man's long-term average values in epidemiologic studies. Between 2005 and 2014, a total of 329 men from a fertility clinic in Boston, Massachusetts, provided 768 semen samples as part of the Environment and Reproductive Health (EARTH) Study. Total sperm count, sperm concentration, morphology, motility, and ejaculate volume were assessed. We used linear mixed models to compare values from men's first semen samples with their long-term averages and to calculate intraclass correlation coefficients for each parameter. We calculated positive predictive values (PPVs) and negative predictive values (NPVs) by comparing agreement in classification according to World Health Organization reference limits. There were no differences in mean semen parameters between men's first samples and the remaining replicates. Intraclass correlation coefficients ranged from 0.61 for morphology to 0.75 for concentration, indicating consistently greater between-man variability than within-man variability. Nevertheless, using 1 sample alone resulted in high NPVs but low PPVs (range, 43%-91%). The average of 2 samples was needed to achieve high PPVs (range, 86%-100%) and NPVs (range, 91%-100%). We conclude that 1 semen sample may suffice for studies aimed at identifying average differences in semen quality between individuals. Studies aimed at classifying men based on World Health Organization reference limits may benefit from collection of 2 or more samples.


Peroxisome proliferator-activated receptor [gamma] agonist provides superior renal protection versus angiotensin-converting enzyme inhibition in a rat model of type 2 diabetes with obesity.
The inbred obese Zucker (ZDF/Gmi, fa/fa) rat develops severe hyperglycemia and also exhibits severe renal disease. In this study, we compared the relative benefits of long-term treatment with angiotensin-converting enzyme inhibition (ACEI) to a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist. Four groups of obese inbred Zucker rats were studied over a 6-month observation period; untreated animals, rats treated with ACEI alone, rats treated with PPARgamma agonist alone, and rats treated with a combination of ACEI and PPARgamma agonist. PPARgamma agonist treatment normalized plasma glucose and led to massive increases in body weight. Both ACEI and PPARgamma agonist were effective in reducing the proteinuria and glomerular and tubular kidney damage. However, the PPARgamma agonist exerted superior renal protection compared with ACEI, in this model of spontaneously occurring chronic renal disease in the diabetic, obese inbred Zucker rat. Of note, although ACEI lowered blood pressure, there was no difference in glomerular blood pressure in any group at the end of the study. The glomerular filtration rate (GFR) was improved by ACEI with a borderline effect of PPARgamma agonist alone. A mild additive protection on GFR and tubulointerstitial damage was seen with the combination. Based on the literature it is likely that the superior protection by PPARgamma agonist versus glomerular and tubular damage as well as proteinuria extends beyond glycemic and lipidmic control and also reflects direct, protective intrarenal actions of the PPARgamma agonists.


Decomposition of poly-beta-hydroxybutyrate by pseudomonads.
Delafield, F. P. (University of California, Berkeley), M. Doudoroff, N. J. Palleroni, C. J. Lusty, and R. Contopoulos. Decomposition of poly-beta-hydroxybutyrate by pseudomonads. J. Bacteriol. 90:1455-1466. 1965.-A number of aerobic pseudomonads capable of using poly-beta-hydroxybutyrate as sole source of carbon have been partially characterized. One was selected for special study and described as a new species, Pseudomonas lemoignei Delafield. This bacterium constitutively produces extracellular digestive enzymes that hydrolyze the polymer to a mixture of d-beta-hydroxybutyrate and the dimeric ester of this acid, as well as an intracellular "dimer hydrolase" which hydrolyzes the dimeric ester. The exoenzymes are excreted during growth, but mainly at its cessation. Metabolism of beta-hydroxybutyrate largely suppresses enzyme excretion and causes a disappearance of excreted enzyme.


Analysis of the morphology of the unipolar endocardial paced evoked response.
In a retrospective study we analyzed the unipolar endocardial evoked response signal (ERS) of 103 patients prior to pacemaker implantation. The objective of this study was to give a complete description of the ERS morphology and to evaluate influences on this morphology of both various electrode characteristics and pacing rate. In addition, spontaneous endocardial signals were studied. The results demonstrate that acute leads had both higher R wave and T wave amplitudes and a faster downslope of the T wave. In the acute leads those with porous titanium carbon coated tips showed a more pronounced T wave. Pacing rate influences the R wave amplitude and the stimulus to T wave interval. Both stimulus to maximum and stimulus to minimum T wave interval show an exponential correlation with the stimulus interval. The interval between maximum and minimum of the T wave and the absolute amplitude of T wave are not influenced by rate. Although there were significant correlations of the spontaneous endocardial signal with the ERS, the predictive value of the spontaneous signal for the ERS morphology is low. Prospective studies will be necessary to confirm the findings in this study.


Bleomycin hypersensitivity in dyskeratosis congenita fibroblasts, lymphocytes, and transformed lymphoblasts.
We studied the responses of several dyskeratosis congenita (DC) cell lines to the DNA strand-cleaving and base-damaging agent bleomycin. Fibroblasts, peripheral blood lymphocytes, and transformed lymphoblasts of six DC patients and an obligate DC heterozygote showed more chromatid breaks than did respective controls exposed to various concentrations of bleomycin during the G2 phase of the cell cycle (P less than 0.0001). Unsynchronized DC fibroblasts in culture also showed decreased survival, compared to normals, following bleomycin treatment. DC lymphocytes treated with bleomycin for the final 24 h of culture showed more chromatid- and chromosome-type damage than did normals (P less than 0.0001) or G0-treated DC lymphocytes. Spontaneous chromosome breakage was normal in all six DC cell lines. The ability to distinguish affected and heterozygous DC cells without spontaneous chromosome instability from normals on the basis of their bleomycin hypersensitivity provides a marker for future studies of the pathogenesis of this disorder.


Dark-blood MRI of the thoracic aorta with 3D diffusion-prepared steady-state free precession: initial clinical evaluation.
The purpose of this study was to compare the performance of 3D diffusion-prepared balanced steady-state free precession (SSFP) imaging with that of 3D contrast-enhanced MR angiography in evaluation of the thoracic aorta. Twenty-one patients with indications for contrast-enhanced MR angiography and diffusion-prepared SSFP of the thoracic aorta were involved in this retrospective chart review study conducted with 1.5-T MRI. Two observers scored the quality of the contrast-enhanced MR angiographic and diffusion-prepared SSFP images on the basis of depicting the thoracic aorta. Image quality scores and diametric measurements of the aorta from both image sets were compared. Diametric measurements of the thoracic aorta showed a strong linear association (r = 0.971, p < 0.0001; regression line indifferent from line of equality, p < 0.05). The aortic root was better visualized with contrast-enhanced MR angiography (image quality score, 3.6 +/- 0.9 vs 3.0 +/- 0.8 of 5; p < 0.05); however, the aortic wall was better visualized with diffusion-prepared SSFP (image quality score, 4.4 +/- 0.6 vs 1.9 +/- 0.3 of 5; p < 0.0001). Three-dimensional diffusion-prepared SSFP yields better image quality than 3D contrast-enhanced MR angiography in evaluation of the thoracic aortic wall and appears to be a useful adjunct to 3D contrast-enhanced MR angiography for assessing aortic abnormalities before administration of a contrast agent.


Impact of severe infections in SLE: an observational study from the Spanish national registry.
Infections are a common complication of SLE. Our objective was to evaluate their causes and impact on the survival of patients with SLE. Analysis of the admissions and death causes in patients diagnosed with SLE from the Spanish Hospital Discharge Database and the infection-related deaths of the Spanish population from the National Statistical Institute, between 2016 and 2018.Only infections recorded as the main diagnosis were analysed (severe or clinically relevant infection). Among 18 430 admissions in patients with SLE, disease activity was the cause of admission in 19% of all patients and infection in 15%. However, infection was the main cause of death (25%) while SLE activity was responsible for only 6% of deaths (p<0.001). Severe infection exceeded SLE as a cause of death for patients dying at ages between 40-59 (23% vs 4%, p<0.001), 60-79 (26% vs 6%, p<0.001) and older than 80 years (25% vs 6%, p<0.001). Infection was the cause of death in 8% of the Spanish population, a significantly lower rate when compared with patients with SLE (p<0.001). Compared with the general population, infections were the highest relative cause of death in patients with SLE, particularly at younger ages: 40% vs 3% for those below 20 years old (p<0.01), 33% vs 4% between 20 and 39 (p<0.001), 23% vs 5% between 40 and 59 (p<0.001), 26% vs 5% between 60 and 79 (p<0.001) and 25% vs 9% for those older than 80 years (p<0.001). Our nationwide study confirms that infections are the leading cause of death in SLE in Spain, with the highest proportion occurring in young patients with lupus compared with the general population of the same age range.


Clinical and virological response to adefovir dipovixil for lamivudine-resistant HBeAg-negative hepatitis B.
Adefovir dipivoxil (ADV), a new nucleotide analogue, has demonstrated activity against lamivudine-resistant HBV both in vivo and in vitro. Herein, we present eight lamivudine-resistant patients with chronic anti-HBe positive hepatitis B treated orally with adefovir dipivoxil at 10 mg/die to evaluate the efficacy and safety of this drug and to determine the possible development of clinical ADV resistance. After 48 weeks of therapy, 4/8 (50%) patients demonstrated a complete response with normalization of alaninoaminotransferase levels (ALT, normal value < 40 IU/L) and undetectable serum HBV- DNA (< 100 copies/ml tested by a PCR assay). In 3/8 subjects (37.5%), we observed a partial response with a > 50% reduction of both ALT and HBV DNA levels. Only one patient did not respond. Adefovir was well-tolerated and no patient presented adverse events related to treatment; there were no changes in renal parameters. We conclude that in patients with anti-HBe positive chronic hepatitis B resistant to lamivudine, a 48-week ADV treatment resulted in significant biochemical and virological improvement without major adverse effects.


Transient exposure of fibroblast growth factor-2 induced proliferative but not destructive changes in mouse knee joints.
Fibroblast growth factor-2 (FGF-2) has the potential to regenerate damaged articular cartilage tissue due to its exerting anabolic effects on chondrocytes. However, FGF-2 is involved in pathogenesis of rheumatoid arthritis, where the joint is destructed. The study aims at clarifying the effects of FGF-2 on joints. When radiolabeled FGF-2 was injected into knee joints of C57Bl/10 mice, a transient binding was observed in the superficial and intermediate zones of the articular cartilage as well as in the synovium and perichondrium. An FGF-2 injection (5 microg) caused synovial hyperplasia adjacent to the articular cartilage on day 7, cartilage formation adjacent to the articular cartilage on day 14, and osteophyte on day 21. The intensity of safranin-O staining of the articular cartilage increased on day 14. These changes were dose-dependent. No destructive changes in the joints were observed. In a joint, transient exposure of FGF-2 caused proliferative changes, but not destructive changes.


Developing clinical performance measures based on the Dialysis Outcomes Quality Initiative Clinical Practice Guidelines: process, outcomes, and implications.
The National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Practice Guidelines established a widely accepted set of recommendations for high-quality dialysis care. To enhance the End-Stage Renal Disease Core Indicators Project, an ongoing effort to assess and improve dialysis care in the United States, the Centers for Medicare and Medicaid Services (CMS) commissioned a project to develop clinical performance measures (CPMs) based on the NKF-DOQI guidelines. The CMS contracted with Qualis Health, a private nonprofit organization serving as a Medicare Quality Improvement Organization, to facilitate a 9-month project to develop dialysis CPMs with the participation of a broad range of stakeholders from the renal community. Work groups were established to develop CPMs addressing 4 areas: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access management, and anemia management. The NKF-DOQI guidelines were prioritized based on the strength of the evidence supporting the guidelines, the feasibility of developing performance measures, and the significance of the areas addressed to the quality of care delivered to dialysis patients. Expert panels developed data specifications, sampling approaches, data-collection tools, and analytic strategies. Sixteen CPMs were developed based on 22 of 114 NKF-DOQI guidelines. After establishing reliability through field-testing of data-collection instruments, the CPMs were applied to a sample of 8,838 randomly selected hemodialysis patients and 1,650 randomly selected adult peritoneal dialysis patients in summer 1999. The development of CPMs based on the NKF-DOQI Clinical Practice Guidelines for dialysis care was accomplished in a timely and effective manner by engaging a broad range of stakeholders and technical experts. The CPMs are important tools to assess and improve the quality of dialysis care in the United States. Few comparable efforts exist in other fields of medicine.


Structure of the nuclease domain of ribonuclease III from M. tuberculosis at 2.1 A.
RNase III enzymes are a highly conserved family of proteins that specifically cleave double-stranded (ds)RNA. These proteins are involved in a diverse group of functions, including ribosomal RNA processing, mRNA maturation and decay, snRNA and snoRNA processing, and RNA interference. Here we report the crystal structure of the nuclease domain of RNase III from the pathogen Mycobacterium tuberculosis. Although globally similar to other RNase III folds, this structure has some features not observed in previously reported models. These include the presence of an additional metal ion near the catalytic site, as well as conserved secondary structural elements that are proposed to have functional roles in the recognition of dsRNAs.


Periodontal and restorative considerations in rotary gingival curettage.
A relatively new surgical gingival retraction technique has been discussed from a periodontal point of view. This technique provides a method of enlarging the gingival sulcus so preparation margins for cast restorations can be visualized and accurately recorded in impression material. The preoperative health of the periodontium is an important consideration when selecting this technique. The attachment apparatus must be free of inflammation and the marginal gingiva must have an acceptable width and a high degree of keratinization. If these criteria are met, a hemorrhage-free opened gingival trough will be easily and consistently obtained. The following restorative sequence was suggested and should be used and completed one step at a time: pulp therapy, buildup restoration, supragingival casting preparation, rotary gingival curettage, reversible hydrocolloid wet field impression technique, indirect provisionalization, placement of final cast restoration. These recommendations were based on the compatibility with the periodontal tissues. Such periodontal compatibility is evident in consistent postoperative tissue healing. There is minimal or no change in the position of the epithelial attachment and location of the crest of the free marginal gingiva. Histological and longitudinal clinical research studies are needed on the rotary gingival curettage technique. Clinical studies on the reversible hydrocolloid wet field technique would also be helpful. Until such evidence is available, my clinical experience indicates that rotary gingival curettage is an excellent technique producing predictable and gratifying results if the treatment planning and restorative sequence suggested in this paper are followed.


Clinical and pathologic effects of a modified technique for application of spiral prostheses to the cervical trachea of dogs.
A modified surgical technique for application of extraluminal polypropylene spiral prostheses (PSP) to the trachea was developed. A portion of the segmental blood supply to the collapsed segment of trachea was maintained by fenestrating rather than completely dissecting the right lateral pedicle. Polypropylene spiral prostheses were applied to the cervical trachea of 12 dogs (group I) via the modified technique and to 12 dogs (group II) with the identical surgical dissection but without PSP applied. Clinical abnormalities included mild coughing in group I dogs and swelling of the incisions in both groups. Limited necrosis and moderate degeneration and inflammation were observed histologically in both groups. Pathologic changes were worse in the caudal cervical segment of the trachea. Mucosal regeneration was present on day 10 in both groups. Transmural tracheal necrosis was not observed. The modified technique for application of PSP is recommended by the authors because it provides adequate surgical exposure and the blood supply preserved by segmentally dissecting the right lateral pedicle is adequate to maintain tracheal viability.


The spectrum of clinical paediatric endocrinology: 28 years of referrals to an individual consultant.
To review referrals throughout the career of an individual paediatric endocrinologist. A retrospective cohort study in metropolitan clinics in Queensland analysed details of all 9062 patients aged<18 years referred between January 1980 and December 2007 to determine the proportion of diagnoses in major disease categories and changes in referral patterns over time. Short stature (29%), type-1 diabetes mellitus (20%) and pubertal disorders (12%) accounted for most cases, with thyroid disorders (7%), obesity (6%), tall stature (5%) and hypothalamic-pituitary disorders (4%) the next commonest. An organic cause for short stature, early puberty, late puberty, tall stature and obesity was found in 39%, 32%, 19%, 15% and 6% of cases, respectively. Boys were more likely to present with short stature or delayed puberty, and girls with tall stature and early puberty. Substantially fewer boys than girls were diagnosed in infancy with congenital adrenal hyperplasia, suggesting that some may be dying undiagnosed. Comparisons between 1980 and 1984, and 2000-2004 revealed increases in the percentage of referrals for type-1 diabetes mellitus (particularly in the young), early puberty, hypothalamic-pituitary and bone disorders, and decreases in those for short and tall stature. Disorders of growth and puberty accounted for 52% of referrals and many have an organic cause. A neonatal screening programme for congenital adrenal hyperplasia is overdue. Changing attitudes to short and tall stature and a profound increase in new cases of diabetes mellitus indicate that substantially greater resources for treatment of childhood diabetes mellitus will be required in future.


Guidelines for prevention of cardiovascular disease in women: a summary of recommendations.
Cardiovascular disease (CVD) is a major cause of mortality in women. The first evidence-based guidelines for the prevention of CVD in women were developed in 2004 and updated this year. The 2007 guidelines place more emphasis on women's overall lifetime coronary heart disease risk, as opposed to short-term absolute risk, than did the 2004 recommendations. Depending on the criteria met, women are classified as being at high risk, at risk, or at optimal risk. The authors provide an overview of the recommendations in the 3 different categories: lifestyle interventions, major risk factor interventions, and preventive drug interventions.


Citreamicins with potent gram-positive activity.
Two new xanthone antibiotics, citreamicin delta (1) and epsilon (2), with potent activity against Gram-positive pathogens including multidrug-resistant Staphylococcus aureus (MDRSA) were discovered. Compounds 1 and 2 exhibited MIC values < 1 microg/mL versus a number of resistant strains. The compounds were obtained from EtOAc extracts of Streptomyces vinaceus and were purified by countercurrent chromatography and reversed-phase HPLC. Their structures were elucidated using primarily NMR and mass spectroscopy.


Social Media-Based Secondary Distribution of Human Immunodeficiency Virus/Syphilis Self-testing Among Chinese Men Who Have Sex with Men.
Social media and secondary distribution (distributing self-testing kits by indexes through their networks) both show strong promise to improve human immunodeficiency virus (HIV) self-testing uptake. We assessed an implementation program in Zhuhai, China, which focused on the secondary distribution of HIV/syphilis self-test kits among men who have sex with men (MSM) via social media. Men aged ≥16 years, born biologically male, and ever had sex with another man were recruited as indexes. Banner ads on a social media platform invited the participants to apply for up to 5 self-test kits every 3 months. Index men paid a deposit of US$15/kit refundable upon submitting a photograph of a completed test result via an online submission system. They were informed that they could distribute the kits to others (referred to as "alters"). A total of 371 unique index men applied for 1150 kits (mean age, 28.7 [standard deviation, 6.9] years), of which 1141 test results were returned (99%). Among them, 1099 were valid test results; 810 (74%) were from 331 unique index men, and 289 tests (26%) were from 281 unique alters. Compared to index men, a higher proportion of alters were naive HIV testers (40% vs 21%; P < .001). The total HIV self-test reactivity rate was 3%, with alters having a significantly higher rate than indexes (5% vs 2%; P = .008). A total of 21 people (3%) had a reactive syphilis test result. Integrating social media with the secondary distribution of self-test kits may hold promise to increase HIV/syphilis testing coverage and case identification among MSM.


[Circadian aspects of acetylsalicylic acid induced injury and protective effect of ranitidine on the the upper gastrointestinal tract].
Circadian Aspects of Acetylsalicylic Acid Induced Injury and Protective Effect of Ranitidine on the Upper Gastrointestinal Tract. In a randomised parallel double-blind study the gastric and duodenal effects of 300 mg acetylsalicylic acid (ASA, CAS 50-78-2) daily in the presence and absence of 150 mg ranitidine (Zantic, CAS 66357-35-5) daily was evaluated in 32 healthy volunteers undergoing upper gastrointestinal endoscopy. Drugs were taken over a period of 7 days either at 8 a.m. (n = 16) or at 8 p.m. (n = 16). Endoscopic controls were performed at entry and repeated after 7 days of treatment. At entry both groups showed comparable mucosal damages: 8 a.m. group: ASA/placebo 0.8 +/- 0.1 (stomach) and 0.1 +/- 0.1 (duodenum): ASA/ranitidine 1.0 +/- 0.0 (stomach) and 0.07 +/- 0.06 (duodenum). 8 p.m. group: ASA/placebo 0.9 +/- 0.06 (stomach) and 0.1 +/- 0.09 (duodenum). ASA/ranitidine 0.8 +/- 0.08 (stomach) and 0.07 +/- 0.06 (duodenum). After 7 days of treatment the lesions score increased in the ASA/Placebo group in the 8 a.m. group to 9.1 +/- 1.1 (stomach) and 2.7 +/- 1.0 (duodenum), and in the 8 p.m. group to 10.9 +/- 1.1 (stomach) and to 3.9 +/- 0.9 duodenum). The corresponding values in the ASA/ranitidine group were 2.6 +/- 0.8 (stomach) and 0.2 +/- 0.08 (duodenum) (8 a.m.) and 4.8 +/- 0.8 (stomach) and 0.3 +/- 0.1 (duodenum) (8 p.m.). There was no statistical difference between the morning- and the evening dose of ASA. In addition, ranitidine protection was also time-independent.(ABSTRACT TRUNCATED AT 250 WORDS)


Reproductive performance following midtrimester termination of pregnancy.
The aim of the study was to determine the impact of midtrimester abortion with extra-amniotic PGE(2) on future fertility and reproduction. Two hundred and fifteen women were enrolled. The mean induction-to-abortion interval was 21.3 h. The complication rate was 11.7%. Twenty women (9.3%) were lost to follow-up, 82 patients (38.1%) used contraception. Spontaneous pregnancy occurred in 110 out of 113 women who desired fertility (97%). Three patients were defined as infertile but conceived following treatment. The average time between the abortion and the next conception was 15.9 months (range 1-77 months). Seventy patients (63.7%) delivered at term. Premature delivery occurred in 18 patients (16.4%). Eighteen women aborted spontaneously in the first and 3 in the second trimester. One extrauterine pregnancy occurred. Second-trimester abortion with extra-amniotic PGE(2) is a safe procedure with a low rate of complication. Apparently it does not affect future fertility, but may be associated with an increased rate of premature deliveries in future gestations.