Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That Targets Specific Cone Subtypes.
Human Crb1 is implicated in some forms of retinal degeneration, suggesting a role in photoreceptor maintenance. Multiple Crumbs (Crb) polarity genes are expressed in vertebrate retina, although their functional roles are not well understood. To gain further insight into Crb and photoreceptor maintenance, we compared retinal cell densities between wild-type and Tg(RH2-2:Crb2b-sfEX/RH2-2:GFP)pt108b transgenic zebrafish, in which the extracellular domain of Crb2b-short form (Crb2b-sfEX) is expressed in the retina as a secreted protein, which disrupts the planar organization of RGB cones (red, green, and blue) by interfering with Crb2a/2b-based cone-cone adhesion. We used standard morphometric techniques to assess age-related changes in retinal cell densities in adult zebrafish (3 to 27 months old), and to assess effects of the Crb2b-sfEX transgene on retinal structure and photoreceptor densities. Linear cell densities were measured in all retinal layers in radial sections with JB4-Feulgen histology. Planar (surface) densities of cones were determined in retinal flat-mounts. Cell counts from wild-type and pt108b transgenic fish were compared with both a "photoreceptor maintenance index" and statistical analysis of cell counts. Age-related changes in retinal cell linear densities and cone photoreceptor planar densities in wild-type adult zebrafish provided a baseline for analysis. Expression of Crb2b-sfEX caused progressive and selective degeneration of RGB cones, but had no effect on ultraviolet-sensitive (UV) cones, and increased numbers of rod photoreceptors. These differential responses of RGB cones, UV cones, and rods to sustained exposure to Crb2b-sfEX suggest that Crb-based photoreceptor maintenance mechanisms are highly selective.


[Therapy of tuberculosis].
The treatment of tuberculosis consists of a combination of at least 3 antituberculosis drugs to prevent occurrence of resistance. Each drug is discussed in detail. Different therapy regimens are described taking into consideration ethnic origin, compliance and underlying diseases of the patients. Standard therapy consists of a short course therapy including rifampicin, isoniazid and pyrazinamide for 6 months. Duration of therapy is extended in immunocompromised patients and in particular organ manifestations of the disease (i.e. meningitis etc.). Intermittent therapy improves compliance of the patients. Four-drug-regimens are recommended until the results of drug susceptibility tests are available in patients originating of countries with high prevalence of resistant strains.


The effect of storage delay and storage temperature on orthopaedic surgical samples contaminated by Staphylococcus Epidermidis.
Prosthetic Joint Infection (PJI) is a rare but devastating complications with high morbitity and mortality. The identification of the causal microorganism remains crucial and determines therapeutic strategies and success. Microbiology cultures remain the common method to diagnose PJI. Unfortunately, 14% of intra-articular punctures remain negative after culture. The microorganisms are best detected by inoculation of microbiology samples in blood culture bottles (Bactec), or after sonication of the implant and polymerase chain reaction (PCR). The identification of the causal microorganism remains crucial and determines therapeutic success. This study was conducted to assess the effect of culture lead time and sample storage temperature on the detection of the pathogen. We obtained bone fragments from femoral heads during primary arthroplasty. Bone fragments were contaminated with a strain of Staphylococcus epidermidis. Four set-ups with different combinations of storage delay and storage temperature were tested. Our study shows the need to cultivate as soon as possible and optimally within 2h after the completion of sampling. Temporary storage in a refrigerator at 4°C also appears to have a positive influence on bacterial viability. At present, these conclusions concern only the Staphylococcus Epidermidis. Others studies are requested to generalize this conclusion to other bacteria.


Online case-based learning for medical students as a teaching method for biochemistry at King Abdulaziz University amid COVID-19 pandemic (a study conducted in 2021).
Online case-based learning (CBL) is a method used by King Abdulaziz University to teach medical students in their preclinical years. The use of CBL in basic sciences is important for enabling medical students to correlate basic sciences with future clinical practice. This study implemented online CBL for biochemistry teaching as part of the medical genetic module for 3rd-year preclinical students. Teaching during the study was completely online because of restricted precautions caused by the COVID-19 pandemic, except for practical sessions that were held on campus. The case was presented to the students involved in prenatal screening and diagnosis. Students were guided to learn and discuss the biochemical tests used for prenatal screening and diagnosis and their clinical importance. They were divided into two groups: the control group was given an online lecture and the intervention group was given an online CBL session before the lecture. The online lecture was given to both groups simultaneously by the same instructor, and then 10 MCQs tests were distributed to both groups after the lecture, and their test scores were compared. A 10-question survey was administered to the intervention group to assess their perception of the online CBL session after the test. A significant difference was found between the intervention and control groups regarding test scores (p < 0.001), and most students found the online CBL session enjoyable and motivating.


Surfactant Engineering and Its Role in Determining the Performance of Nanoparticulate Organic Photovoltaic Devices.
The fabrication of organic photovoltaics (OPVs) from non-hazardous nanoparticulate (NP) inks offers considerable promise for the development of eco-friendly large-scale printed solar modules. However, the typical NP core-shell morphology (driven by the different donor/acceptor affinities for the surfactant used in NP synthesis) currently hinders the photovoltaic performance. As such, surfactant engineering offers an elegant approach to synthesizing a more optimal intermixed NP morphology and hence an improved photovoltaic performance. In this work, the morphology of conventional sodium dodecyl sulfate (SDS) and 2-(3-thienyl) ethyloxybutylsulfonate (TEBS)-stabilized poly(3-hexylthiophene) (P3HT) donor:phenyl-C61-butyric acid methyl ester (PC61BM) acceptor NPs is probed using scanning transmission X-ray microscopy, UV-vis spectroscopy, grazing-incidence X-ray diffraction, and scanning electron microscopy. While the SDS-stabilized NPs exhibit a size-independent core-shell morphology, this work reveals that TEBS-stabilized NPs deliver an intermixed morphology, the extent of which depends on the particle size. Consequently, by optimizing the TEBS-stabilized NP size and distribution, NP-OPV devices with a power conversion efficiency that is ∼50% higher on average than that of the corresponding SDS-based NP-OPV devices are produced.


Schiff base thorium(iv) and uranium(iv) chloro complexes: synthesis, substitution and oxidation chemistry.
New tetradentate Schiff base chloro complexes of U(iv) and Th(iv) are prepared by salt metathesis approaches. These compounds undergo clean salt metathesis with NaN3 to generate stable pseudo-trans azide compounds. The uranium dichloro complex also undergoes 2 e- oxidation with excess NaNO2 to generate the uranyl derivative. All classes of complexes are characterized by single crystal X-ray diffraction and NMR spectroscopy.


Arylpiperazine derivatives of 3-propyl-beta-tetralonohydantoin as new 5-HT1A and 5-HT2A receptor ligands.
A series of new analogues of 3-[3-(4-arylpiperazinyl)-propyl]-cyclo-hexane-1',5-spirohydantoin (2), with aromatic ring fused in amide moiety (4-9) were synthesized and evaluated for affinity at 5-HTIA and 5-HT2A receptors. The influence of the substitution mode in the phenyl ring of phenylpiperazine moiety on the affinity for both receptors has been discussed. The most potent 5-HTIA (9, Ki = 53 nM) and 5-HT2A (4, 6, 8 and 9; Ki = 14-76 nM) ligands were evaluated in in vivo tests. The obtained results indicate that all in vivo tested compounds showed pharmacological profile of 5-HT2A antagonists. Additionally, a m-CF3 derivative (9), behaved like a partial agonist (agonist of pre- and antagonist of postsynaptic) of 5-HTIA receptors and may offer a new lead for the development of potential psychotropic agents.


Prevalence of taurodontism found in radiographic dental examination of 1,200 young adult Israeli patients.
The prevalence of taurodontism was studied radiographically in 1,200 young adult Israeli patients. In order to differentiate taurodont teeth from normal teeth, three types of taurodontism (meso-, hypo- and hypertaudodontism) were defined in biometric terms, using radiographic features of molar morphology. All three types according to Shaw's classification were seen. Taurodontism was found to occur in 5.6% of 1,200 individuals and in 1.5% of the 10,204 molar teeth examined. The mandibular second molar was found to be the most prone, being involved in two thirds of all cases found. Hypertaurodontism was found only in three cases, in the third molars. The conditions was seen to involve single and multiple teeth, both unilaterally and bilaterally, with the latter being most predominant.


Surgical Treatment of Angular Pott's Kyphosis with Posterior Approach, Pedicular Wedge Osteotomy and Canal Widening.
It has been observed that the correction of severe posttuberculous angular kyphosis is still a challenge, mainly because of the neurologic risk. Nine patients were reviewed after surgery (mean follow-up 18 months). There were 2 thoracic, 4 thoraco-lumbar and 3 lumbar kyphosis. The mean age at surgery was 23. Clinical results were evaluated by the Oswestry Disability Index (ODI) and by the neurologic evaluation. Preoperative, postoperative and final follow-up X-rays were assessed. The surgery included a posterior approach with cord release and correction by transpedicular wedge osteotomy and widening of the spinal canal. Average kyphotic angulation was 72° before surgery, 10° after surgery and 12° at follow-up. Three out of four patients with neural deficit showed improvement. Neurologic complications included a transitory quadriceps paralysis, likely by foraminal compression of the root. A posterior transpedicular wedge osteotomy allows a substantial correction of the kyphosis, more by deflexion than by elongation, with limited neurologic risks. However it is mandatory to widely enlarge the spinal canal on the levels adjacent to the osteotomy, in order to allow the dura to expand backwards.


Measuring the safety climate in NHS organisations.
This article discusses the differences between organisational culture and organisational climate, and provides an overview of the relationship between safety culture and safety climate within these wider concepts. The article concludes with a brief description of an initiative to test a safety climate measurement tool for use in NHS organisations.


Resection of isolated pelvic recurrences after colorectal surgery: long-term results and predictors of improved clinical outcome.
Recurrence in the pelvis after resection of a rectal or rectosigmoid cancer presents a dilemma. Resection offers the only reasonable probability for cure, but at the cost of marked perioperative morbidity and potential mortality. Clinical decision making remains difficult. Patients who underwent resection with curative intent for isolated pelvic recurrences after curative colorectal surgery from 1988 through 2003 were reviewed retrospectively. Clinical and pathological factors, salvage operations, and complications were recorded. The primary measured outcome was overall survival. Univariate and multivariate analyses were conducted to identify prognostic factors of improved outcome. Ninety patients underwent an attempt at curative resection of a pelvic recurrence; median follow-up was 31 months. Complications occurred in 53% of patients. Operative mortality occurred in 4 (4.4%) of 90 patients. Median overall survival was 38 months, and estimated 5-year survival was 40%. A total of 51 of 86 patients had known recurrences (15 local, 16 distant, 20 both). Multivariate analysis revealed that preoperative carcinoembryonic antigen level and final margin status were statistically significant predictors of outcome. The resection of pelvic recurrences after colorectal surgery for cancer can be performed with low mortality and good long-term outcome; however, morbidity from such procedures is high. Low preoperative carcinoembryonic antigen and negative margin of resection predict improved survival.


Divergence in the Saccharomyces species' heat shock response is indicative of their thermal tolerance.
The Saccharomyces species have diverged in their thermal growth profile. Both S. cerevisiae and S. paradoxus grow at temperatures well above the maximum growth temperature of S. kudriavzevii and S. uvarum, but grow more poorly at lower temperatures. In response to thermal shifts, organisms activate a stress response that includes heat shock proteins involved in protein homeostasis and acquisition of thermal tolerance. To determine whether Saccharomyces species have diverged in their response to temperature we measured changes in gene expression in response to a 12°C increase or decrease in temperature for four Saccharomyces species and their six pairwise hybrids. To ensure coverage of subtelomeric gene families we sequenced, assembled and annotated a complete S. uvarum genome. All the strains exhibited a stronger response to heat than cold treatment. In response to heat, the cryophilic species showed a stronger response than the thermophilic species. The hybrids showed a mixture of parental stress responses depending on the time point. After the initial response, hybrids with a thermophilic parent were more similar to S. cerevisiae and S. paradoxus, and the S. cerevisiae × S. paradoxus hybrid showed the weakest heat shock response. Within the hybrids a small subset of temperature responsive genes showed species specific responses but most were also hybrid specific. Our results show that divergence in the heat shock response is indicative of a strain's thermal tolerance, suggesting that cellular factors that signal heat stress or resolve heat induced changes are relevant to thermal divergence in the Saccharomyces species.


Muddy perceptions/dirty water: messages for clearing the visions of the public and the powerful.
Globalism does not usually work when it comes to spreading the word about water! There is no one formula for explaining water issues to the public or to public officials. Sometimes you should go to reporters. Sometimes you should focus on educating editors. Sometimes you concentrate on educating teachers, sometimes the business community, bureaucrats or elected officials. Sometimes your message concentrates on fisheries, sometimes health, sometimes tourism. Often, you will want to emphasize something else--even sales of genetic material that might be dependent on biodiversity. In short, your message must be adapted to the local circumstance. Your methodology will depend on whether you must stimulate immediate action, or whether you have the luxury of pushing a longer-term message. The Web opens many new possibilities. Cost of Web distribution is low. The Web offers a combination of many effective storytelling tools such as audio, video, and animation. Multi-lingual materials are easier to prepare than for film. But at this stage of Web development it may be more efficient to provide material to existing publications' Web sites and to NGOs and official sites, than to establish special stand-alone Web sites. I propose a "resource" Web site for those who have responsibility for water projects. The site would contain articles and explanatory material provided by media organizations, attracted by a modest contest-and-prize system.


Res Ipsa Loquitur: a step along the road to liability without fault.
Traditionally, courts have required that the plaintiff prove the negligence of medical defendants through expert testimony. Res ipsa loquitur, on the other hand, allows juries to infer negligence from the circumstances surrounding the injury. The tension between those two propositions is obvious. It is incongruous to allow a lay jury to infer a proposition that generally demands expert proof.


Mycophenolate mofetil: a novel immunosuppressant in the treatment of dystrophic epidermolysis bullosa, a randomized controlled trial.
No effective treatment has been found for epidermolysis bullosa dystrophica (EBD). To evaluate the efficacy and safety mycophenolate mofetil (MMF) in treating EBD. This randomized controlled double-blinded study included 35 patients with severe generalized EBD. Patients were randomly divided into two groups: group I (18 patients) received cyclosporine therapy (5 mg/kg/day) and group II (17 patients) received MMF therapy (500-1500 mg/day). Clinical assessment was made weekly for 3 months from the start of the treatment. Patients were assessed by measuring the extent of the disease, the % of improvement, assessing the number of new blister formation and the time of complete healing of new blisters. Side effects were recorded when detected. The % of improvement in the disease extent was statistically significantly higher (p = 0.009) in group I (mean ± SD: 59.21 ± 22.676) than in group II (mean ± SD: 44.03 ± 25.71). As regards the number of new blisters and the rate of healing of blisters, there was no statistically significant difference between both groups (p = 0.693 and 0.404, respectively). No serious side effects were reported. MMF seems to be a good therapeutic option for the long-term treatment of EBD, it can be a good alternative for patients who cannot tolerate cyclosporine.


Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease.
Emerging evidence suggests that gut microbiome composition alterations affect neurodegeneration through neuroinflammation in the pathogenesis of Parkinson's disease (PD). Here, we evaluate gut microbiota alterations and host cytokine responses in a population of Taiwanese patients with PD. Fecal microbiota communities from 80 patients with PD and 77 age and gender-matched controls were assessed by sequencing the V3-V4 region of the 16S ribosomal RNA gene. Diet and comorbidities were controlled in the analyses. Plasma concentrations of IL-1β, IL-2, IL-4, IL-6, IL-13, IL-18, GM-CSF, IFNγ, and TNFα were measured by a multiplex immunoassay and relationships between microbiota, clinical characteristics, and cytokine levels were analyzed in the PD group. We further examined the cytokine changes associated with the altered gut microbiota seen in patients with PD in another independent cohort of 120 PD patients and 120 controls. Microbiota from patients with PD was altered relative to controls and dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores (rho = 0.637 [95% confidence interval 0.474 to 0.758], P < 0.01). Altered microbiota was correlated with plasma concentrations of IFNγ and TNFα. There was a correlation between Bacteroides and plasma level of TNFα (rho = 0.638 [95% CI: 0.102-0.887], P = 0.02); and a correlation between Verrucomicrobia abundance and plasma concentrations of IFNγ (rho = 0.545 [95% CI - 0.043-0.852], P = 0.05). The elevated plasma cytokine responses were confirmed in an additional independent 120 patients with PD and 120 controls (TNFα: PD vs. control 8.51 ± 4.63 pg/ml vs. 4.82 ± 2.23 pg/ml, P < 0.01; and IFNγ: PD vs. control: 38.45 ± 7.12 pg/ml vs. 32.79 ± 8.03 pg/ml, P = 0.03). This study reveals altered gut microbiota in PD and its correlation with clinical phenotypes and severity in our population. The altered plasma cytokine profiles associated with gut microbiome composition alterations suggest aberrant immune responses may contribute to inflammatory processes in PD.


[Results of Russian Hospital Chronic Heart Failure Registry in Three Subjects of Russian Federation].
Aim of the RUssian hoSpital Heart Failure Registry (RUS-HFR) was to analyze clinical and epidemiological characteristics, application of modern drug and non-drug therapy among hospitalized patients with systolic chronic heart failure (CHF) in 3 subjects of Russian Federation. We conducted a prospective multicenter observational study in 3 cardiological centers (Petersburg, Orenburg, Samara) in which we recruited patients aged 18-75 years with left ventricular ejection fraction less or equal 40% without ongoing myocardial infarction or pulmonary thromboembolism. Between October 2012 and June 2014 we included 524 patients (mean age 60 years, >79% men) mostly with NYHA class III CHF. Main etiological factors were ischemic heart disease and arterial hypertension, which was not corrected by the time of admission in 20-40.7% of patients. Portions of patients who had undergo the myocardial revascularization, surgery because of valvular heart defects, and implantation of permanent pacemaker including device for cardiac resynchronizing therapy were 11-41, 0-4, and 0-19.5%, respectively. In up to 25% of patients therapy with one of main medications or diuretic was initiated after hospitalization. At discharge 82.3-8.3, 76.3-95.8, 65.9-81.1, 80.7-94.6% of patients received ACEI/ARB, -adrenoblockers, MRA, diuretic therapy, respectively. Implantation of cardioverter ICD/CRT, ICD and heart transplantation were considered indicated in 0-21.2 and 0-6.6% of patients, respectively. Duration of hospitalization was 26+/-14, 15+/-10, and 13+/-5 bed-days in Petersburg, Orenburg, and Samara, respectively. Compared with data obtained 10 years earlier portrait of a patient with in general remained unchanged. However portion of patients who had undergone cardio-surgical and electrophysiological interventions became tangible, and numbers of patients receiving therapy with ACEI/ARB, -adrenoblockers, and MRA became comparable with those in European registries. Significant deviations from guidelines on drug therapy were revealed at prehospital stage; and high-technology methods of therapy were insufficiently often recommended in participating hospitals. Portion of hospitalizations not related to acute decompensation was 5-37%, while duration of such hospitalizations as well as hospitalizations because of acute decompensation of CHF significantly exceeded this parameter in EU and USA. Absence of obligatory drug therapy prior to admission in a part of patients in RUS-HF raises questions on correction of patients compliance and on creation of a system of specialized ambulatory surveillance of CHF patients after discharge from hospital.


Single-incentive selective associations produced solely as a function of compound-stimulus conditioning context.
Barpressing was maintained in a tone-plus-light (TL) condition in 2 groups of rats by shock-related contingencies and in 2 other groups by food-related contingencies. Responding ceased in TL absence (TL). Contingency arrangements made TL hedonically positive, relative to TL, for 1 shock group and for 1 food group and hedonically negative for 1 shock group and for 1 food group. In a stimulus-element test, the visual modality was dominant when TL was hedonically positive, whereas auditory control increased when TL was negative, irrespective of the reinforcers involved. Within-incentive contingency manipulations produced selective associations hitherto ascribed to stimulus-reinforcer interactions, suggesting that biological constraints on learning may operate at the level of conditioned psychological states.


Continuity of care among patients newly initiated on second-generation oral or long-acting injectable antipsychotics during a schizophrenia-related inpatient stay.
Maintaining continuity of care after schizophrenia-related hospitalization is challenging for patients and healthcare providers and systems. Prior evidence suggests that second-generation long-acting injectable antipsychotics (SGLAIs) may reduce the risk of treatment nonadherence and readmission versus oral atypical antipsychotics (OAAs). Therefore, quality measures were compared between patients initiated on SGLAIs and OAAs in the United States. Adults newly initiated on an SGLAI or OAA during a schizophrenia-related inpatient stay were identified in HealthVerity databases (01/2015-12/2020); the index date was the hospital discharge date. Patients had continuous health insurance coverage for pharmacy and medical services for 6 months pre-admission and post-discharge from the inpatient stay and ≥1 pharmacy or medical claim (i.e. treatment as indicated by the observed insurance claims) for an antipsychotic other than the index SGLAI or OAA in the 6 months pre-admission. Antipsychotic use and adherence, and schizophrenia-related readmissions and outpatient visits were compared during the 6-month period post-discharge. Characteristics between cohorts were balanced using inverse probability weights. Post-discharge, only 36.9% and 40.7% of weighted SGLAI (N = 466) and OAA (N = 517) patients had ≥1 pharmacy or medical claim for the antipsychotic initiated during the inpatient stay, among whom SGLAI patients were 4.4 times more likely to be adherent to that antipsychotic compared to OAA patients (p < .001). Additionally, SGLAI patients were 2.3 and 3.0 times more likely to have a pharmacy or medical claim for and be adherent to any antipsychotic relative to OAA patients (including index antipsychotic; all p < .001). Within 7 and 30 days post-discharge, 1.7% and 13.0% of SGLAI patients and 4.1% and 12.6% of OAA patients had a readmission. Further, SGLAI patients were 51% more likely to have an outpatient visit compared to OAA patients (p = .044). Less than half of patients initiated on antipsychotics during a schizophrenia-related inpatient stay continued the same treatment post-discharge. However, SGLAI patients were more likely to be adherent to the initiated antipsychotic and to have an outpatient visit, which may suggest improved continuity of care post-discharge relative to OAA patients.


Lest we forget. Illuminating lived experience of the Covid-19 pandemic and lockdown.
The COVID-19 pandemic and associated 'lockdowns' profoundly impacted people's lives in 2020-2021 and beyond. This study sought to understand unique person-centred insights into health and wellbeing during the restrictive measures in the United Kingdom and to enable us to remember and give testimony to these lived experiences. Using photo-methods, participants from a larger cohort study which tracked people's behaviours during the pandemic were invited to share photographs and short text to visually illustrate their ephemeral and unique COVID-19 experiences. In total 197 participants shared 398 photographs. Using a critical realist approach in our design and analysis, we sought to gain an alternative viewpoint on what 'lockdown' and the pandemic meant. Our major findings revealed starkly contrasting experiences illustrated in our two major themes. Firstly loss, including ambiguous losses and a sense of loss, loss of freedoms and death. Secondly, salutogenesis (what makes us well) whereby participants were able to draw on assets which helped to keep them well by maintaining social connection, 'making the best of it', reconnecting with nature and appreciating the outdoors, creativity for pleasure and faith. Our findings illuminate widely differing experiences and indicate the powerful effect of assets that were perceived by our participants to protect their wellbeing. Understanding differential vulnerability will be essential going forward to target resources appropriately to those who have the least control over their lives, those with the greatest vulnerabilities and least assets which in turn could support a self-perpetuating recovery.


Transnasal hypophysectomy.
A transnasal trans-sphenoidal surgical approach to the pituitary gland is described. The operative and post-operative experiences with the use of this technique on 21 patients with hormone-dependent malignant disease are reported. In 2 patients the procedure was abandoned because of intrasellar haemorrhage and in 1 an empty sella was found. Fifteen patients developed diabetes insipidus and 1 patient died in the postoperative period.


Response to Erich Loewy: commentary.
The capacity to suffer, the vulnerability with respect to suffering, confers on all animals with that capacity (not just human beings) a prima facie right not to be caused suffering. Nurturing in order to stave off such suffering is the first act of the community toward the individual, primarily in infancy. Hence for Loewy, autonomy, the gradual growth of self-determination in individuals, is grounded in a broader moral commitment of the community, that of beneficence. This is the critical point in his argument, for it represents a wholesale critique of modern libertarianism. Libertarians, in contrast to Loewy's argument, seem to ground the nature of the community in the prima facie right of autonomy. For Loewy, the community not only has an obligation to refrain from harming individuals (nonmaleficence), but it also has an active duty to ameliorate and prevent, as far as possible, the suffering of its members. Thus, if there is a social contract, it is one of nurturing one another to overcome the vulnerability of suffering, not primarily one of protecting autonomy. This is most significant for clinical ethics as well. Once the primary obligation to ameliorate suffering is no longer necessary, when the individual loses or does not have the primary moral worth prompted by the capacity to suffer, then secondary and symbolic obligations emerge. Loewy is thereby able to suggest a "calculus" of moral worth, wherein our obligations to individuals in a permanent vegetative state or to anencephalics (almost always the individual will have lost the capacity to suffer through some cerebral event) must be weighed against other primary obligations. Although Loewy admits that grounding clinical ethics in the capacity to suffer might be "thin," it nevertheless prompts serious discussion about the nature of the "good" in good clinical ethics decisions.


Immunostimulating properties of intragastrically administered Acetobacter-derived soluble branched (1,4)-beta-D-glucans decrease murine susceptibility to Listeria monocytogenes.
We previously found that AC-1, an extracellular polysaccharide, produced by Acetobacter xylinum and composed of (1,4)-beta-D-glucan with branches of glucosyl residues, showed a strong activity to induce production of interleukin-12 (IL-12) p40 and tumor necrosis factor alpha by macrophages in vitro via Toll-like receptor 4 (TLR-4) signaling. In the present study, we examined the effect of oral administration of AC-1 on protective immunity against Listeria monocytogenes. Mice were given AC-1 or phosphate-buffered saline (PBS) intragastrically 2 days before, on the day of, and 2 days after an intraperitoneal inoculation of L. monocytogenes. The survival rate of AC-1-treated mice was significantly improved and bacterial growth in AC-1-treated mice was severely retarded compared to those of PBS-treated mice after infection with L. monocytogenes. IL-12 p40 levels in serum and magnitudes of CD4+ Th1 and CD8+ Tc1 responses against Listeria antigen were significantly higher in AC-1-treated mice than in PBS-treated mice. The effect of AC-1 on antilisterial activity was diminished in C3H/HeJ mice carrying mutated TLR-4. Thus, AC-1, a potent IL-12 inducer through TLR-4, enhanced protective immunity against L. monocytogenes via augmentation of Th1 responses. These results suggest that infectious processes driven by intracellular microorganisms could be prevented to develop by the (1,4)-beta-D-glucan.


Time-reversal acoustic focusing system as a virtual random phased array.
This paper compares the performance of two different systems for dynamic focusing of ultrasonic waves: conventional 2-D phased arrays (PA) and a focusing system based on the principles of time-reversed acoustics (TRA). Focused ultrasound fields obtained in the experiments with the TRA focusing system (TRA FS), which employs a liquid-filled reverberator with 4 piezotransducers attached to its wall, are compared with the focused fields obtained by mathematical simulation of PAs comprised from several tens to several hundreds of elements distributed randomly on the array surface. The experimental and simulated focusing systems had the same aperture and operated at a frequency centered about 600 kHz. Experimental results demonstrated that the TRA FS with a small number of channels can produce complex focused patterns and can steer them with efficiency comparable to that of a PA with hundreds of elements. It is shown that the TRA FS can be realized using an extremely simple means, such as a reverberator made of a water-filled plastic bottle with just a few piezotransducers attached to its walls.


Rickettsia (Rickettsiales: Rickettsiaceae) Vector Biodiversity in High Altitude Atlantic Forest Fragments Within a Semiarid Climate: A New Endemic Area of Spotted-Fever in Brazil.
Rickettsioses are re-emerging vector-borne zoonoses with a global distribution. Recently, Rickettsia sp. strain Atlantic rainforest has been associated with new human spotted-fever (SF) cases in Brazil, featuring particular clinical signs: eschar formation and lymphadenopathy. These cases have been associated with the tick species, Amblyomma ovale From 2010 until 2015, the Brazilian Health Department confirmed 11 human SF cases in the Maciço de Baturité region, Ceará, Brazil. The present study reports the circulation of Rickettsia spp. in vectors from this entirely new endemic area for SF. A total of 1,727 ectoparasites were collected in this area from the environment, humans, and wild and domestic animals. Samples (n = 887) were screened by polymerase chain reaction (PCR), targeting the gltA and ompA rickettsial genes. Sequencing and phylogenetic analyses of gltA gene amplicons were carried out for 13 samples positive for both screening PCRs. Fragments of gltA and ompA from three samples were cloned, sequenced, and analyzed further. A. ovale and Rhipicephalus sanguineus specimens, collected from dogs, were found to be infected with Rickettsia sp. str. Atlantic rainforest, suggesting the importance of dogs in the epidemic cycle. Candidatus Rickettsia andeanae, Rickettsia felis, and Rickettsia bellii were also found infecting ticks and fleas in five municipalities, demonstrating the broad diversity of rickettsiae in circulation in the studied area. This study reports, for the first time, evidence of infection with Rickettsia sp. strain Atlantic rainforest in A. ovale and R. sanguineus in Ceará, and Ca. R. andeanae in an Atlantic rainforest environment of Brazil.


A Comparative Study on the Population Fitness of Three Strains of Nilaparvata lugens (Hemiptera: Delphacidae) Differ in Eye Color-Related Genes.
The brown planthopper, Nilaparvata lugens (Stål), is a destructive insect pest on rice throughout Asia. As a visible genetic marker, red eye mutant colony of brown planthopper is a valuable material. Here, we established the near-isogenic lines, NIL-BB and NIL-rr, through mating red eye females to brown eye brothers for eight successive generations. Biological experiments showed that NIL-BB had big fitness cost; however, NIL-rr had comparable survival and fertility parameters with BB, a normal laboratory brown planthopper strain. Significantly lower number eggs per female and egg hatchability were the key factors resulting in big fitness cost of NIL-BB. The population trend indexes of BB, NIL-rr, and NIL-BB were 52.18, 43.80, and 4.19, respectively. Real-time PCR study suggested that the poorer fertility of NIL-BB was not mediated by the differential expression of genes relating to oogenesis. The stronger fitness of NIL-rr compared with NIL-BB may be caused by the eye mutant gene or its closely linked genes having stronger compensation ability for reproduction. The comparable fitness of NIL-rr with BB indicated that NIL-rr may be used in field research. The NIL-BB strain with significantly declined fecundity and survival ability can be used as study model for the signal pathways relating to fecundity.


The descriptive epidemiology of standing activity during free-living in 5412 middle-aged adults: the 1970 British Cohort Study.
Standing is often classified as light-intensity physical activity, with potential health benefits compared with sitting. Standing is, however, rarely captured as an independent activity. To better understand free-living standing behaviour at a population level, we incorporated a gold standard postural allocation technique into a national cohort study. Participants (n=5412, aged 46.8±0.7 years) from the 1970 British Cohort Study were fitted with a water-proofed thigh-mounted accelerometer device (activPAL3 micro) worn 24 hours continuously over 7 days (90.7% provided at least 3 full days). We examined the correlates of free-living standing during waking hours. Total daily standing time averaged 4.6±1.5 h/d, accounting for 29% of waking hours, which was largely (98.7%) accumulated in bouts lasting less than 30 min. In mutually adjusted models, male sex, obesity, diabetes, professional occupation, poor self-rated health and disability were associated with lower device-measured standing times. Middle-aged people in Britain spent a surprisingly large proportion of the day in activities involving standing. Standing merits attention as a health-related posture and may represent a potential target for public health intervention.


Confidence bounds for the estimation of the volume phase fraction from a single image in a nickel base superalloy.
We propose an image-based framework to evaluate the uncertainty in the estimation of the volume fraction of specific microstructures based on the observation of a single section. These microstructures consist of cubes organized on a cubic mesh, such as monocrystalline nickel base superalloys. The framework is twofold: a model-based stereological analysis allows relating two-dimensional image observations to three-dimensional microstructure features, and a spatial statistical analysis allows computing approximate confidence bounds while assessing the representativeness of the image. The reliability of the method is assessed on synthetic models. Volume fraction estimation variances and approximate confidence intervals are computed on real superalloy images in the context of material characterization.


Use of volumetric computerized tomography as a primary outcome measure to evaluate drug efficacy in the prevention of peri-prosthetic osteolysis: a 1-year clinical pilot of etanercept vs. placebo.
Although total hip replacement (THR) is amongst the most successful and beneficial medical procedures to date, long-term outcomes continue to suffer from aseptic loosening secondary to peri-prosthetic osteolysis. Extensive research over the last two decades has elucidated a central mechanism for osteolysis in which wear debris generated from the implant stimulates inflammatory cells to promote osteoclastogenesis and bone resorption. The cytokine tumor necrosis factor alpha (TNFalpha) has been demonstrated to be central to this process and is considered to be a leading target for intervention. Unfortunately, even though FDA approved TNF antagonists are available (etanercept), currently there are no reliable outcome measures that can be used to evaluate the efficacy of a drug to prevent peri-prosthetic osteolysis. To the end of developing an effective outcome measure, we evaluated the progression of lesion size in 20 patients with established peri-acetabular osteolysis (mean=29.99 cm(3), range=2.9-92.7 cm(3)) of an uncemented primary THR over 1-year, using a novel volumetric computer tomography (3D-CT) technique. We also evaluated polyethylene wear, urine N-telopeptides and functional assessments (WOMAC, SF-36 and Harris Hip Score) for comparison. At the time of entry into the study baseline CT scans were obtained and the patients were randomized to etanercept (25 mg s.q., twice/week) and placebo in a double-blinded fashion. CT scans, urine and functional assessments were also obtained at 6 and 12 months. No serious adverse drug related events were reported, but one patient had to have revision surgery before completion of the study due to aseptic loosening. No remarkable differences between the groups were observed. However, the study was not powered to see significant drug effects. 3D-CT data from the 19 patients was used to determine the mean increase in lesion size over 48 weeks, which was 3.19 cm(3) (p<0.0013). Analysis of the urine N-telopeptides and functional assessment data failed to identify a significant correlation with wear or osteolysis. In conclusion, volumetric CT was able to measure progression of osteolysis over the course of a year, thus providing a technology that could be used in therapeutic trials. Using the data from this pilot we provide a model power calculation for such a trial.


Home-Based Exercise for People With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.
Exercise performed at home could be a useful therapy for people with chronic kidney disease. This systematic review and meta-analysis aimed at describing the characteristics, main findings, methodological quality, and adherence rate reported in the existent randomized controlled trials that have provided information regarding the impact of home-based exercise programs on people with chronic kidney disease. Electronic databases (MEDLINE/PubMed, SPORTDiscus, Scopus, and CENTRAL) were searched up to April 2021, using the keywords: "Exercise"; "Home"; "Kidney Disease." Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was adopted. Jadad scale and Cochrane's tool were used to assess the methodological quality and risk of bias. Out of the 14 studies finally selected, 11 were included in the meta-analysis and most presented high methodological quality. The meta-analysis showed significant effects of home-based exercise on fitness and quality of life, but a little impact on renal function. Although exercise performed at home was mostly feasible and safe, adherence was not high and a considerable number of dropouts were observed. Home-based exercise has positive effects on the fitness' level and on the quality of life on people with chronic kidney disease. Future studies are needed to identify whether exercise performed at home is a better physical therapy option than center-based exercise.


Accessibility of the functional groups of chitosan aerogel probed by FT-IR-monitored deuteration.
Transmission FT-IR spectroscopy allowed us to monitor the deuteration of wafers of chitosan aerogel and xerogel by D2O vapor at room temperature. The complete deuteration of the alcohol and amine groups of the aerogel (surface area 175 m2 g(-1) as measured by N2 volumetry) confirmed the high accessibility of the functional groups of the polymer. The xerogel (surface area 5 m2 g(-1)) was only partially deuterated in more severe conditions. The isotopic shift of the deuterated groups allowed us to confirm or revise some attributions of infrared bands of chitosan.


Antineutrophil cytoplasmic antibody subtypes in children and adolescents after ileal pouch-anal anastomosis for ulcerative colitis.
Perinuclear antineutrophil cytoplasmic antibodies occur frequently in adult patients with chronic pouchitis after colectomy and ileal pouch-anal anastomosis for ulcerative colitis. The purpose of the study was to determine the prevalence of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in children and adolescents who undergo colectomy and ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis. Five groups of children and adolescents (age, <20 years) were studied, with the following histories: acute pouchitis and history of ulcerative colitis; chronic pouchitis and history of ulcerative colitis; pouchitis with Crohn's disease features and a history of ulcerative colitis; no pouchitis and a history of ulcerative colitis; and familial adenomatous polyposis, with or without pouchitis. Antineutrophil cytoplasmic antibody levels and titers were detected in postoperative sera by enzyme-linked immunosorbent assay, and positive results were subtyped by indirect immunofluorescence. The frequency of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in patients with a history of ulcerative colitis were 67% and 15%, compared with a 0% presence in patients with familial adenomatous polyposis (p < 0.001). There was no significant correlation between the frequency of perinuclear antineutrophil cytoplasmic antibodies and ulcerative colitis patient subgroups (patients with and without pouchitis, 66% and 75%). Similarly, there was no significant correlation between the frequency of cytoplasmic antineutrophil cytoplasmic antibodies among ulcerative colitis patient subgroups (patients with and without pouchitis, 19% and 8%). The frequency of cytoplasmic antineutrophil cytoplasmic antibody in patients with Crohn's disease features (50%), was increased, but this difference was not significant. There is a high frequency of perinuclear antineutrophil cytoplasmic antibodies in children and adolescents who undergo ileal pouch-anal anastomosis for ulcerative colitis, whether or not they have pouchitis. The frequency of cytoplasmic antineutrophil cytoplasmic antibody is lower in this patient population. Additional studies will be required to determine whether the presence of cytoplasmic antineutrophil cytoplasmic antibody is associated with the postoperative development of features of Crohn's disease.


Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations.
Despite the availability of several potent HER2-directed targeted agents, primary and acquired resistance continues to influence patient outcomes in HER2-positive breast cancer. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor in late-phase clinical development. This review article focuses on neratinib in the treatment of HER2-positive breast cancer - early and metastatic stage - and HER2-mutant breast cancer, with particular emphasis on the pharmacokinetics and pharmacodynamics of the drug. The phase III ExteNET trial shows that neratinib improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in early-stage HER2-positive breast cancer, and in particular HER2+/HR+ tumors. Survival data are awaited. The investigational role of neratinib in high-risk patients or conversely in de-escalation dual regimens with other anti-HER2 therapies and without chemotherapy are of interest. Phase II trials show that neratinib has efficacy, either as monotherapy or in combination with other chemotherapeutic or endocrine agents, in patients with HER2-positive metastatic breast cancer and in tumors harboring HER2 mutations. The role of neratinib in therapeutic algorithms of HER2-positive patients, as well as delaying CNS events, awaits the results of ongoing trials such as NALA. Diarrhea, the main toxicity of neratinib, can be effectively managed with early loperamide prophylaxis.


[Evaluation of ambient air pollution in Tashkent].
The paper presents the results of studying and evaluating the ambient air pollution in Tashkent in 2003-2005 according to the City Center of State Sanitary-and-Epidemiological Surveillance Service. In Tashkent, the proportion of chemically unstandard (higher than the maximum permissible concentrations) samples of ambient air was ascertained to higher than that in Uzbekistan towns as a whole. Soot, acrolein, formaldehyde, dust, benzene, aromatic carbohydrates, and nitric oxide are the most significant hygienic ingredients. The pollution levels are different in various districts of the city.


Erector spinae plane block with catheter infusion for analgesia in a patient undergoing transaxillary first rib resection.
Analgesia for first rib resection can be challenging with short- and long-term consequences for patients such as acute distress, difficulty participating in physiotherapy and chronic pain. We report utilising an erector spinae plane block with a continuous infusion catheter as analgesia for a transaxillary first rib removal in a patient with venous thoracic outlet syndrome (Paget-Schroetter syndrome). We could find no reports of erector spinae plane block in transaxillary rib resection, and a limited number of reports using a paravertebral approach to analgesia for this procedure. In our case, an erector spinae plane block provided effective analgesia, allowing the patient to participate freely in postoperative physiotherapy; no complications of erector spinae plane block were encountered. Further research into the safety and efficacy of erector spinae plane block for first rib resection is warranted.


[A case of antigranulocyte antibody positive Felty's syndrome and its efficacy of plasmapheresis].
The patient is a 44-year-old female case of RA having a history of 10 years after onset, being admitted due to fever accompanied by granulocytopenia. By laboratory findings, WBC was 1,900/mm3, CRP 5+, RA 2+, RAHA 80 times, LE cells positive, antinuclear antibody strongly positive, granulocyte-specific antinuclear antibodies positive, and granulocyte specific cytotoxicity test strongly positive. Examination of bone marrow smears revealed, the cell numbers tended to decrease in the neutrophil maturity phase. The case was diagnosed as Felty's syndrome because of the obvious splenomegaly and leukopenia. Administration of 30 mg/day of prednisolone was not sufficient in effect, and plasmapheresis was conducted concomitantly. As a result, the granulocyte count increased and the granulocyte cytotoxicity titer was lowered. It is hence suggested that the antigranulocyte antibodies are responsible for the mechanism of granulocytopenia in this case, and the possibility of promotion of destruction in the periphery was inferred, and it is accordingly considered useful to combine administration of small dose of adrenocortical steroid preparation with plasmapheresis for the treatment of this disease.


Segmentation and Quantitative Analysis of Apoptosis of Chinese Hamster Ovary Cells from Fluorescence Microscopy Images.
Accurate and fast quantitative analysis of living cells from fluorescence microscopy images is useful for evaluating experimental outcomes and cell culture protocols. An algorithm is developed in this work to automatically segment and distinguish apoptotic cells from normal cells. The algorithm involves three steps consisting of two segmentation steps and a classification step. The segmentation steps are: (i) a coarse segmentation, combining a range filter with a marching square method, is used as a prefiltering step to provide the approximate positions of cells within a two-dimensional matrix used to store cells' images and the count of the number of cells for a given image; and (ii) a fine segmentation step using the Active Contours Without Edges method is applied to the boundaries of cells identified in the coarse segmentation step. Although this basic two-step approach provides accurate edges when the cells in a given image are sparsely distributed, the occurrence of clusters of cells in high cell density samples requires further processing. Hence, a novel algorithm for clusters is developed to identify the edges of cells within clusters and to approximate their morphological features. Based on the segmentation results, a support vector machine classifier that uses three morphological features: the mean value of pixel intensities in the cellular regions, the variance of pixel intensities in the vicinity of cell boundaries, and the lengths of the boundaries, is developed for distinguishing apoptotic cells from normal cells. The algorithm is shown to be efficient in terms of computational time, quantitative analysis, and differentiation accuracy, as compared with the use of the active contours method without the proposed preliminary coarse segmentation step.


Incidence and management of phantom limb pain according to World Health Organization analgesic ladder in amputees of malignant origin.
Antidepressants and anticonvulsants are currently considered to be the drug treatment of choice for neuropathic pain. Opioids are effective in relieving neuropathic pain, including phantom pain in the early postoperative course. The present study of 42 cancer patients with limb amputation was conducted to determine the incidence of phantom limb pain and phantom sensation and to test the utility of the World Health Organization 3-step analgesic ladder in phantom limb pain management. Patients were monitored monthly for the first 2 months postoperatively and every 2 months thereafter for 2 years. The World Health Organization analgesic ladder was followed for pain management. The patients complaining of phantom sensation, phantom pain, and stump pain decreased from 69%, 60%, and 31%, respectively, at 1 month to 32%, 32%, and 5%, at the end of 2 years with the addition of opioids. The World Health Organization analgesic ladder played significant role in phantom limb pain management.


Comparison of ESBL--and AmpC producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA) isolated from migratory and resident population of rooks (Corvus frugilegus) in Austria.
In order to test whether rooks (Corvus frugilegus) represent good indicators for the potential circulation of antibiotics in their native habitat, two populations with different migratory behavior were tested for the presence of beta-lactamase producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA). In all, 54 and 102 samples of fresh feces of a migratory and a resident population were investigated. A total of 24 and 3 cefotaxime-resistant enterobacterial isolates were obtained from the migratory and resident population, respectively. In these isolates CTX-M-1 (n = 15), CTX-M-3 (n = 3), and CTX-M-15 (n = 3) genes were detected. TEM-1 and OXA-1 were associated with CTX-M in 3 and 2 isolates, respectively. In two E. coli isolates CMY-2 could be detected, where from one isolate displayed an overexpression of chromosomal AmpC as well. Among E. coli isolates the most common phylogenetic group was A (n = 11) and ST1683 (n = 5). In one E. coli of B2-ST131 the rfbO25b locus was detected. Three Enterobacter isolates were stably derepressed AmpC-producers. In five samples of the migratory population, PVL positive MRSA could be isolated. Two isolates were typed SCCmec IVa, spa type t127, and ST1. Three isolates carried a SCCmec type IVc, with spa type t852 and ST22. The highly significant difference of the occurrence of antibiotic resistance between the migratory population from eastern Europe compared to resident population in our study indicates that rooks may be good indicator species for the evaluation of environmental contamination with antibiotic resistant bacteria, especially due to their ecology, foraging behavior and differing migratory behavior.


Impact of antithrombotic therapy on postpancreatectomy hemorrhage in 7116 patients: A project study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.
We previously reported an association between antithrombotic therapy and an increased risk of postpancreatectomy hemorrhage (PPH). To validate our findings, we conducted a large-scale multicenter retrospective study from 63 high-volume centers in Japan. Between 2015 and 2018, 7116 patients who underwent pancreatectomy were enrolled. The antithrombotic group consisted of 920 patients (12.9%) who received preoperative antithrombotic agents including aspirin, clopidogrel, ticlopidine, prasugrel, warfarin, and direct oral anticoagulants. PPH occurred in 235 (3.3%) of the patients. The incidence of PPH and mortality were significantly higher in the antithrombotic group than in the control group (5.7 vs. 3.0% and 2.2 vs. 0.9%, respectively; both p < .001). In multivariate analysis, a history of antithrombotic use was an independent risk factor for grade C PPH (p = .036). In the antithrombotic group, PPH tended to be delayed in the patients with restarting antithrombotic therapy. Notably, the occurrence of delayed PPH after restarting antithrombotic therapy was observed only when antithrombotic therapy was restarted within 10 days after pancreatectomy. This multicenter study demonstrated that a history of antithrombotic use was a significant risk factor for PPH and mortality. In particular, the resumption of antithrombotic therapy in the early postoperative period should be done with caution.


Calling, permission, and fulfillment: the interembodied experience of breastfeeding.
Drawing on examples from in-depth interviews with 49 women, in this article we aim to open up a discursive space for women and health professionals to begin to explore the phenomenon of the interembodied experience of breastfeeding. Although acknowledging that social dimensions partially constitute the lived body, we further the view that the lived body's understanding is embedded in contexts far more complex than those that can be represented by language. We argue that women's narratives of their breastfeeding experience contained instances of the body "understanding" its emotional task at a prelogical, preverbal level. We identified three central, iterative dimensions of the phenomenon—calling, permission, and fulfillment—that occurred prereflexively in the protected space provided by the mother, a space that was easily disrupted by unsupportive postnatal practices. We offer this eidetic understanding and conceptual framework and suggest that it provides new (less damaging) subject positions and ways of behaving.


[Study on the iodine nutrition and iodine deficiency disorders status in pasturing areas of Tibet-a non-epidemic area of iodine deficiency disorders in serious iodine deficiency district].
To explore the status of iodine nutrition and iodine deficiency disorders in the pasturing areas and agricultural regions in Tibet. 30 families were selected respectively in pastoral Dangxiong county and agricultural Qushui county of Lasa. Drinking water and edible salt were collected for testing the iodine contents. In each type of the following populations including children aged 8 - 10, women of child-bearing age and male adults, 50 subjects were randomly sampled to examine their urinary iodine contents. Among them, 50 children and 50 women were randomly selected for goiter examination by palpation. Water iodine content was less than 2 µg/L, both in pasturing area and in agricultural areas. There was no iodized salt used in the families of pasturing areas, while 90% people consumed iodized salt in agricultural areas. The median of urinary iodine in pasturing area was 50.2 µg/L, significantly lower than that of agricultural area (193.2 µg/L). However, the goiter rate of children and women in pasturing area was significantly lower than that in agricultural area. Although iodine intake of populations in pasturing area of Tibet was severely deficient, there was no epidemic of Iodine Deficiency Disorders. This phenomenon noticed by the researchers deserved further investigation.


Giant omental lipoma in a child.
Omental lipomas are extremely rare tumors of childhood. We report a case of solitary giant lipoma of the omentum in a child, successfully managed by complete excision, without any recurrence on follow-up study.


Hepatotoxicity and pneumotoxicity of styrene and its metabolites in glutathione S-transferase-deficient mice.
Styrene is known to be hepatotoxic and pneumotoxic in rodents, and these adverse effects are related to its metabolism. Mice deficient in the enzymes responsible for both the activation and detoxification of styrene are useful in examining this relationship more closely. In the current study, mice deficient in glutathione S-transferase P1P2(-/-) (GST(-/-)) were compared with wild-type mice. Similar changes in serum sorbitol dehydrogenase, as an indicator of hepatotoxicity, and bronchioalveolar levels of protein, cells, and lactate dehydrogenase, as indicators of pneumotoxicity, were observed after styrene administration. Glutathione depletion followed a similar pattern. The administration of the toxic metabolite, styrene oxide, which is a direct substrate for glutathione metabolism, and 4-vinylphenol, which is a minor metabolite but is more potent than either styrene oxide, yielded results similar to those of styrene. The results indicate that either other isoforms of glutathione S-transferase are more important than the P1P2 form in styrene detoxification or that this pathway contributes in only a minor way to styrene detoxification, compared to other pathways.


Coverage of complex tissue defects following open cervicothoracic spine surgery with a lower trapezius island myocutaneous flap-an interdisciplinary approach.
The study design is a clinical case series. The objective of this study was to present the concept and efficacy of the lower trapezius island myocutaneous flap (LTIMF) for management of complex wound healing disorders following open cervicothoracic spine surgery. Wound healing disturbances with myocutaneous defects after open spine surgery at the cervical and upper thoracic spine are well-described complications. In severe cases, plastic reconstructive coverage is often required as a last resort. A review of all adult patients with deep wound dehiscence and tissue defects following open cervicothoracic spine surgery, who were managed with plastic surgery reconstruction using a LTIMF at our institution, was conducted. Synopses of these cases are presented. Seven patients with a mean age of 73 years ± 13 (range 50 to 89 years) were included in this case series. Six out of seven patients had instrumented posterior fusion added to their decompression. All patients were managed with a LTIMF for wound coverage. No spinal implants were removed prior to LTIMF surgery. The mean follow-up was 5.2 months (± 5.4 months). No major flap failure occurred, and all patients presented with satisfactory cosmetic results. The only minor complication was development of a sterile subcutaneous seroma in two patients, which were successfully managed by puncture and aspiration. The LTIMF is an effective and reliable salvage treatment option for spine surgery patients offering stable coverage of deep tissue defects resulting from complex wound healing disorders at the cervical and upper thoracic spine.


[Standardize and pragmatism- the key to promote the healthy development of obesity and metabolic surgery in China].
After more than half a century of development, obesity and metabolic surgery in western countries has become a complete surgical specialties, but the introduction of obesity and metabolic surgery was only 10 years old in China. The surgical treatment of obesity and related metabolic diseases, especially obesity of type 2 diabetes has been recognized and acknowledgd by the majority of surgical colleagues and patients as a new direction of development. The current trend of obesity and metabolic surgery is favorable, but there are many problems in the development of obesity and metabolic surgery in China, for example, the surgery nomenclature is not standardized, surgical indications are loosened, the surgical procedure is modified arbitrarily, the evaluation criteria is confusing, the postoperative follow-up protocol is not unified, etc. These problems require the majority of surgical colleagues to work together to make the standards scientifically a nd objectively in accordance with the actual situatioin of our country, so as to promote the healthy development of obesity and metabolic surgery in China.


[Analysis of the reentry status of blood donors with reactive bloodborne pathogen screening markers in Hangzhou City].
Objective: To explore the reentry rate of reactive blood donors in the bloodborne pathogen infection screening in Hangzhou City, and analyze the donation behavior of those who successfully returned. Methods: A retrospective analysis of the return data of blood donors with reactive bloodborne pathogen screening markers was conducted at Zhejiang Provincial Blood Center from June 2017 to May 2022. The reentry process for blood donors with reactive bloodborne pathogen screening markers in Hangzhou City is as follows: after the initial screening period of 6 months, donors can voluntarily apply for return to the blood center. Samples are collected and subjected to routine enzyme-linked immunosorbent assay (ELISA) screening for HBsAg, anti-HCV, HIV Ab/Ag, and anti-TP, as well as a single nucleic acid (HIV/HCV/HBV) test. For samples that show non-reactivity in both ELISA and nucleic acid tests, serum biomarker testing for the reasons of exclusion is performed using chemiluminescence immunoassay (CLIA), and those with non-reactivity are allowed to return. Results: A total of 4 583 reactive blood donors who met the criteria for re-entry applied for reentry, out of which 475 applications were received from donors in the Hangzhou area. Among these, 279 donors were successfully readmitted, resulting in a success rate of 58.74% (279/475). By the end of December 2021, out of the 174 donors who successfully returned, 114 donors chose to donate again. They collectively donated 39 530 ml of whole blood and 1 147.2 therapeutic doses of platelets. Among these, 21 donors once again showed reactivity for pathogen infection biomarkers, accounting for 18.42% (21/114). Conclusion: The reentry strategy has somewhat mitigated the attrition of blood donors. Nevertheless, there are instances where donors who were successfully readmitted show reactivity once more in the screening for pathogen infection biomarkers.


Epistatic SNP interaction of ERCC6 with ERCC8 and their joint protein expression contribute to gastric cancer/atrophic gastritis risk.
Excision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) are two indispensable genes for the initiation of transcription-coupled nucleotide excision repair pathway. This study aimed to evaluate the interactions between single nucleotide polymorphisms of ERCC6 (rs1917799) and ERCC8 (rs158572 and rs158916) in gastric cancer and its precancerous diseases. Besides, protein level analysis were performed to compare ERCC6 and ERCC8 expression in different stages of gastric diseases, and to correlate SNPs jointly with gene expression. Sequenom MassARRAY platform method was used to detect polymorphisms of ERCC6 and ERCC8 in 1916 subjects. In situ ERCC6 and ERCC8 protein expression were detected by immunohistochemistry in 109 chronic superficial gastritis, 109 chronic atrophic gastritis and 109 gastric cancer cases. Our results demonstrated pairwise epistatic interactions between ERCC6 and ERCC8 SNPs that ERCC6 rs1917799-ERCC8 rs158572 combination was associated with decreased risk of chronic atrophic gastritis and increased risk of gastric cancer. ERCC6 rs1917799 also showed a significant interaction with ERCC8 rs158916 to reduce gastric cancer risk. The expressions of ERCC6, ERCC8 and ERCC6-ERCC8 combination have similarities that higher positivity was observed in chronic superficial gastritis compared with chronic atrophic gastritis and gastric cancer. As for the effects of ERCC6 and ERCC8 SNPs on the protein expression, single SNP had no correlation with corresponding gene expression, whereas the ERCC6 rs1917799-ERCC8 rs158572 pair had significant influence on ERCC6 and ERCC6-ERCC8 expression. In conclusion, ERCC6 rs1917799, ERCC8 rs158572 and rs158916 demonstrated pairwise epistatic interactions to associate with chronic atrophic gastritis and gastric cancer risk. The ERCC6 rs1917799-ERCC8 rs158572 pair significantly influence ERCC6 and ERCC6-ERCC8 expression.


Patients' views about cardiac report cards: a qualitative study.
Health care report cards provide stakeholders with information on health care outcomes and other measures of care, and they are most well developed in cardiac care. A necessary first step to ground the development of cardiac report cards (CRCs) is to incorporate the views of stakeholders. Although the views of experts have been described, the views of cardiac patients, arguably the most important stakeholders, have not yet been described. To describe cardiac patients' views about CRCs. Qualitative interviews were conducted with 91 cardiac patients contacted from seven Canadian cardiac care centres. Participants' views regarding CRCs were analyzed and organized into themes. Participants' views were organized into four themes: overall views, purpose, content and dissemination. Participants expressed overwhelmingly positive views about CRCs and thought that CRCs should be used to improve the quality of cardiac care, enhance accountability and improve informed decision-making. They said that they would use CRCs that contained information relevant to patients -- in particular, information about other cardiac patients' experiences. They described a patient-derived framework for the content of CRCs. Participants also described dissemination formats and vehicles that would increase the usefulness of CRCs. The cardiac patients in the present study had positive attitudes about CRCs and would use them if they were designed to be relevant to patients. In particular, the participants wanted CRCs to provide information about other cardiac patients' experiences.


Association of Body Mass Index and Waist Circumference with All-Cause Mortality in Hemodialysis Patients.
In this study based on a large nationally representative sample of Korean adults, we investigated the potential associations of the body mass index (BMI) and waist circumference (WC) with mortality in patients undergoing hemodialysis. We obtained the data of 18,699 participants >20 years of age who were followed up with for 4 years and for whom BMI and WC information were available, using a nationally representative dataset from the Korean National Health Insurance System. Patients were stratified into five levels by their baseline BMI and into six levels by their WC (5-cm increments). A total of 4975 deaths occurred during a median follow-up period of 48.2 months. Participants with a higher BMI had a lower mortality rate than those with a lower BMI. In a fully adjusted Cox regression analysis, being overweight and obese was associated with a significantly lower relative risk of all-cause mortality relative to the reference group. Conversely, the mortality rate was higher among participants with a high WC than among those with a low WC. Participants with the highest WC had a higher risk of mortality, while those with the lowest WC level had a significantly lower risk of mortality. In conclusion, all-cause mortality was positively associated with WC, a measure of abdominal obesity, and inversely associated with BMI, a measure of body volume, in patients undergoing hemodialysis.


The Jamaica asthma and allergies national prevalence survey: rationale and methods.
Asthma is a significant public health problem in the Caribbean. Prevalence surveys using standardized measures of asthma provide valid prevalence estimates to facilitate regional and international comparisons and monitoring of trends. This paper describes methods used in the Jamaica Asthma and Allergies National Prevalence Survey, challenges associated with this survey and strategies used to overcome these challenges. An island wide, cross-sectional, community-based survey of asthma, asthma symptoms and allergies was done among adults and children using the European Community Respiratory Health Survey Questionnaire for adults and the International Study of Asthma and Allergies in Children. Stratified multi-stage cluster sampling was used to select 2, 163 adults aged 18 years and older and 2, 017 children aged 2-17 years for the survey. The Kish selection table was used to select one adult and one child per household. Data analysis accounted for sampling design and prevalence estimates were weighted to produce national estimates. The Jamaica Asthma and Allergies National Prevalence Survey is the first population- based survey in the Caribbean to determine the prevalence of asthma and allergies both in adults and children using standardized methods. With response rates exceeding 80% in both groups, this approach facilitated cost-effective gathering of high quality asthma prevalence data that will facilitate international and regional comparison and monitoring of asthma prevalence trends. Another unique feature of this study was the partnership with the Ministry of Health in Jamaica, which ensured the collection of data relevant for decision-making to facilitate the uptake of research evidence. The findings of this study will provide important data on the burden of asthma and allergies in Jamaica and contribute to evidence-informed planning of comprehensive asthma management and education programs.


A tale of two circuits: CCKNTS neuron stimulation controls appetite and induces opposing motivational states by projections to distinct brain regions.
Cholecystokinin (CCK)-expressing neurons within the nucleus of the solitary tract (CCKNTS) of the mouse are responsive to satiety signals and their chemogenetic activation suppresses appetite. Optogenetic activation of CCKNTS axon terminals within either the parabrachial nucleus (PBN) or the paraventricular nucleus of the hypothalamus (PVH) is sufficient to suppress feeding. An interesting dichotomy has been revealed when assessing the motivational valence of these two circuits. Activating CCKNTS cell bodies is aversive as demonstrated by conditioned taste aversion and place-preference assays. Activation of the CCKNTS→PBN pathway is also aversive; however, stimulating the CCKNTS→PVH pathway is appetitive when assayed using a real-time, place-preference task. Thus, these two projections from CCKNTS neurons reduce food intake through opposite motivational states; one pathway signals positive valence (CCKNTS→PVH) and the other signals negative valence (CCKNTS→PBN).


Lysosomal Biology and Function: Modern View of Cellular Debris Bin.
Lysosomes are the main proteolytic compartments of mammalian cells comprising of a battery of hydrolases. Lysosomes dispose and recycle extracellular or intracellular macromolecules by fusing with endosomes or autophagosomes through specific waste clearance processes such as chaperone-mediated autophagy or microautophagy. The proteolytic end product is transported out of lysosomes via transporters or vesicular membrane trafficking. Recent studies have demonstrated lysosomes as a signaling node which sense, adapt and respond to changes in substrate metabolism to maintain cellular function. Lysosomal dysfunction not only influence pathways mediating membrane trafficking that culminate in the lysosome but also govern metabolic and signaling processes regulating protein sorting and targeting. In this review, we describe the current knowledge of lysosome in influencing sorting and nutrient signaling. We further present a mechanistic overview of intra-lysosomal processes, along with extra-lysosomal processes, governing lysosomal fusion and fission, exocytosis, positioning and membrane contact site formation. This review compiles existing knowledge in the field of lysosomal biology by describing various lysosomal events necessary to maintain cellular homeostasis facilitating development of therapies maintaining lysosomal function.


Associations between heteronormative information, parental support and stress among same-sex mothers in Sweden-A web survey.
The aim was to investigate same-sex mothers' self-assessed experiences of forming a family, and the association between heteronormative information, parental support and parenting stress. A quantitative, cross-sectional study. In a web survey conducted in Sweden in 2019, same-sex mothers (N = 146) with a child aged 1-3 years answered questions about their experiences of forming a family through assisted reproduction and questions about parenting stress. Descriptive statistics describes the process of forming a family. Pearson's correlation analyses and independent sample t tests were used to test hypotheses about heteronormative information, parental support and parenting stress. Same-sex mothers experienced going through assisted reproduction treatment as stressful, and parental groups as not being supportive. Heteronormative information correlated with both lower perceived parental support and higher perceived parenting stress. Non-birth mothers experienced less acknowledgement and support than birthmothers.


Absence of juvenile hormone signalling regulates the dynamic expression profiles of nutritional metabolism genes during diapause preparation in the cabbage beetle Colaphellus bowringi.
Temperate insects have evolved diapause, a period of programmed developmental arrest during specific life stages, to survive unfavourable conditions. During the diapause preparation phase (DPP), diapause-destined individuals generally store large amounts of fat by regulating nutrition distribution for the energy requirement during diapause maintenance and postdiapause development. Although nutritional patterns during the DPP have been investigated at physiological and biochemical levels in many insects, it remains largely unknown how nutritional metabolism is regulated during the DPP at molecular levels. We used RNA sequencing to compare gene expression profiles of adult female cabbage beetles Colaphellus bowringi during the preoviposition phase (POP) and the DPP. Most differentially expressed genes were involved in specific metabolic pathways during the DPP. Genes related to lipid and carbohydrate metabolic pathways were clearly highly expressed during the DPP, whereas genes related to protein metabolic pathways were highly expressed during the POP. Hormone challenge and RNA interference experiments revealed that juvenile hormone via its nuclear receptor methoprene-tolerant mediated the expression of genes associated with nutritional metabolism during the DPP. This work not only sheds light on the mechanisms of diapause preparation, but also provides new insights into the molecular basis of environmental plasticity in insects.


Clinical significance of measuring reticulated platelets in infectious diseases.
This study aimed to explore the association between the percentage of reticulated platelets (RP%) and infection, and analyze the value of combined measurement of RP% with other inflammatory indicators in diagnosing infection. A total of 190 patients with signs and symptoms suspicious of infection were included in the infection group, and 70 healthy subjects with comparable percentages of gender and age were included in the control group. Peripheral white blood cell (WBC) count, percentage of neutrophils (N%), platelet count, C-reactive protein (CRP), procalcitonin (PCT), RP%, and axillary temperature were recorded. Dynamic changes in RP% with infection were measured to analyze the association between RP% and infection. The receiver operating characteristic curve was used to evaluate the value of each inflammatory indicator in diagnosing infection and analyze the diagnostic value of the combined adoption of multiple inflammatory indicators. RP% was significantly higher in the infection group than in the noninfection and control groups. The sensitivity and specificity for diagnosing infection were, respectively, 91.78% and 93.18% when RP% and CRP were used in combination, 90.41% and 90.90% when RP% and PCT were used in combination, and 100% and 100% when RP%, CRP, and PCT were used in combination. RP% changed dynamically with the progression of infection and recovered to lower than 5.5% at 2 to 7 days before the body temperature recovered to a normal level. The diagnostic value of RP% was the highest. A combined use with CRP/PCT could improve the sensitivity and specificity in the early diagnosis of infectious diseases.


Development and public release of a comprehensive hepatitis virus database.
Currently, approximately 44 000 hepatitis C virus (HCV), 11 000 hepatitis B virus (HBV), and 1600 hepatitis E virus (HEV) sequences are available at the International Nucleotide Sequence Database Collaboration (INSDC, previously known as DDBJ/EMBL/GenBank), and the number of these virus sequences is growing rapidly. However, since INDSC is not specialized to hepatitis viruses, it is difficult to retrieve information of virological or clinical interests from it. Thus, it is quite worthwhile to construct a specialized database for the hepatitis virus sequences and to make it accessible to researchers worldwide. We developed a WWW-based database hepatitis virus database (HVDB), which contains all the HCV, HBV, and HEV sequences available at INSDC. In the HVDB, all piece sequences obtained from INSDC are arranged to the genomesequence of each virus. Also given in the database are the phylogenetic relationships of each locus on the genome among variants for each virus. Users of the database can easily retrieve entries (sequences with annotations) of the specific genotype by referring to the phylogenetic relationships or those of specific loci by referring to the genome map information. HVDB provides users with a tool for phylogenetic analysis that can be used in combination with the data retrieval tools. The latest release is publicly accessible at the HVDB website: http://s2as02.genes.nig.ac.jp.


Antiviral effects of pyrrolidine dithiocarbamate on human rhinoviruses.
Human rhinoviruses (HRVs) are the predominant cause of the common cold. The frequency of HRV infections in industrial countries and the lack of effective therapeutical treatment underline the importance of research for new antiviral substances. As viral infections are often accompanied by the generation of oxidative stress inside the infected cells, several redox-active substances were tested as potential antivirals. In the course of these studies it was discovered that pyrrolidine dithiocarbamate (PDTC) is an extremely potent compound against HRV and poliovirus infection in cell culture. Besides the ability to dramatically reduce HRV production by interfering with viral protein expression, PDTC promotes cell survival and abolishes cytopathic effects in infected cells. PDTC also protects cells against poliovirus infection. These effects were highly specific, as several other antioxidants (vitamin C, Trolox, 2-mercaptoethanol, and N-acetyl-L-cysteine) are inactive against HRV infection. Synthesis of HRV proteins and cleavage of eucaryotic initiation factor 4G responsible for host cell shutoff of cellular protein synthesis are severely inhibited in the presence of PDTC.


Polysaccharides from the Sargassum and Brown Algae Genus: Extraction, Purification, and Their Potential Therapeutic Applications.
Brown macroalgae represent one of the most proliferative groups of living organisms in aquatic environments. Due to their abundance, they often cause problems in aquatic and terrestrial ecosystems, resulting in health problems in humans and the death of various aquatic species. To resolve this, the application of Sargassum has been sought in different research areas, such as food, pharmaceuticals, and cosmetics, since Sargassum is an easy target for study and simple to obtain. In addition, its high content of biocompounds, such as polysaccharides, phenols, and amino acids, among others, has attracted attention. One of the valuable components of brown macroalgae is their polysaccharides, which present interesting bioactivities, such as antiviral, antimicrobial, and antitumoral, among others. There is a wide variety of methods of extraction currently used to obtain these polysaccharides, such as supercritical fluid extraction (SFE), pressurized liquid extraction (PLE), subcritical water extraction (SCWE), ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), and microwave-assisted extraction (MAE). Therefore, this work covers the most current information on the methods of extraction, as well as the purification used to obtain a polysaccharide from Sargassum that is able to be utilized as alginates, fucoidans, and laminarins. In addition, a compilation of bioactivities involving brown algae polysaccharides in in vivo and in vitro studies is also presented, along with challenges in the research and marketing of Sargassum-based products that are commercially available.


Liquid chromatography coupled to tandem mass spectrometry for the analysis of acrylamide in typical Spanish products.
This paper describes the use of liquid chromatography coupled to tandem mass spectrometry for the determination of acrylamide in several typical foods produced and consumed in Spain. Christmas sweets, olives, traditionally made potato crisps, pastry products, sweet fritters ("churros") and one of Spain's most famous dishes, Spanish omelette, were selected. Using the mass spectra information provided by an ion trap analyzer in combination with the accurate mass measurements from time-of-flight (TOF) spectrometry a co-extractive interference present in some potato products was identified as valine. A porous graphitic carbon column, which enabled the co-extractive and acrylamide to be separated, and ion trap or triple quadrupole analyzers, depending on the acrylamide concentration, were used to determine this genotoxic compound in foodstuffs. The highest values were found in potato products, sweet fritters, Christmas sweets and pastry products, with values ranging between 70 and 2000 microg/g. Spanish omelette presented relatively low levels, similar to those obtained for dried fruits.


Enhanced expression of caveolin-1 possesses diagnostic and prognostic value and promotes cell migration, invasion and sunitinib resistance in the clear cell renal cell carcinoma.
Caveolin-1 (CAV1) has been identified to be up-regulated in many cancers, including clear cell renal cell carcinoma (ccRCC). However, its potential function is still unclear in ccRCC. In this study, we demonstrated that CAV1 was frequently overexpressed in renal cell carcinoma tissues and cells, and was significantly associated with various clinicopathological parameters. In addition, high CAV1 expression was associated with poor disease-free survival (DFS) rate and could serve as a useful diagnostic indicator in ccRCC patients with different clinicopathological stages. Functional experiments demonstrated that CAV1 knockdown inhibited cell migration and invasion, whereas overexpression of CAV1 promoted cell migration and invasion in ccRCC. Moreover, CAV1 expression was up-regulated in sunitinib-resistant renal cancer cell lines, and its overexpression promoted sunitinib resistance. In general, our results confirm that CAV1 plays an important role in the metastasis of kidney cancer and induces sunitinib resistance, so CAV1 function suppression may become a promising clinical treatment strategy during renal cell carcinoma metastasis and sunitinib resistance.


Acute hepatitis A infection: a predisposing factor for severe leptospirosis.
Leptospirosis is a rare and potentially fatal infection that requires a high index of suspicion for timely diagnosis and treatment. Diagnosis of leptospirosis can be particularly difficult in context of coexistent viral hepatitis. We present a case of Weil's syndrome, in which a concurrent resolving Hepatitis A virus infection was concomitantly diagnosed. Assessment of epidemiologic risk factors and serial serology testing were key in making this diagnosis. The immunologic consequence of the coexistence of these two infections is also discussed. It is likely that hepatitis A infection predisposed our patient's leptospirosis infection to progress to Weil's syndrome.


Evidence for brain morphometric changes during the migraine cycle: a magnetic resonance-based morphometry study.
Neurophysiological investigations have demonstrated that there are unique fluctuations in the migraine brain functional activity between the ictal and interictal periods. Here we investigated the possibility that there are fluctuations over time also in whole brain morphometry of patients affected by episodic migraine without aura (MO).Twenty-four patients with untreated MO underwent 3T MRI scans during (n = 10) or between attacks (n = 14) and were compared to a group of 15 healthy volunteers (HVs). We then performed voxel-based-morphometry (VBM) analysis of structural T1-weighted MRI scans to determine if changes in brain structure were observed over the course of the migraine cycle.Interictally, MO patients had a significantly lower gray matter (GM) density within the right inferior parietal lobule, right temporal inferior gyrus, right superior temporal gyrus, and left temporal pole than did HVs. Ictally, GM density increased within the left temporal pole, bilateral insula, and right lenticular nuclei, but no areas exhibited decreased GM density.These morphometric GM changes between ictal and interictal phases suggest that abnormal structural plasticity may be an important mechanism of migraine pathology. Given the functional neuroanatomy of these areas, our findings suggest that migraine is a condition associated with global dysfunction of multisensory integration and memory processing.


Human T-cell leukemia virus type I Tax activation of NF-kappa B/Rel involves phosphorylation and degradation of I kappa B alpha and RelA (p65)-mediated induction of the c-rel gene.
The tax gene product of human T-cell leukemia virus type I (HTLV-I) is a potent transcriptional activator that both stimulates viral gene expression and activates an array of cellular genes involved in T-cell growth. Tax acts indirectly by inducing or modifying the action of various host transcription factors, including members of the NF-kappa B/Rel family of enhancer-binding proteins. In resting T cells, many of these NF-kappa B/Rel factors are sequestered in the cytoplasm by various ankyrin-rich inhibitory proteins, including I kappa B alpha. HTLV-I Tax expression leads to the constitutive nuclear expression of biologically active NF-kappa B and c-Rel complexes; however, the biochemical mechanism(s) underlying this response remains poorly understood. In this study, we demonstrate that Tax-stimulated nuclear expression of NF-kappa B in both HTLV-I-infected and Tax-transfected human T cells is associated with the phosphorylation and rapid proteolytic degradation of I kappa B alpha. In contrast to prior in vitro studies, at least a fraction of the phosphorylated form of I kappa B alpha remains physically associated with the NF-kappa B complex in vivo but is subject to rapid degradation, thereby promoting the nuclear translocation of the active NF-kappa B complex. We further demonstrate that Tax induction of nuclear c-Rel expression is activated by the RelA (p65) subunit of NF-kappa B, which activates transcription of the c-rel gene through an intrinsic kappa B enhancer element. In normal cells, the subsequent accumulation of nuclear c-Rel acts to inhibit its own continued production, indicating the presence of an autoregulatory loop. However, the pathologic action HTLV-I Tax leads to the deregulated and sustained nuclear expression of both NF-kappa B and c-Rel, a response that may contribute to HTLV-I-induced T-cell transformation.


Dose-response relationship of recent antidepressants in the short-term treatment of depression.
Antidepressant drugs are widely recommended for the treatment of depressive disorders, and finding the "right dose for the right patient" is an important issue. Whatever antidepressant is prescribed, a proportion of adult patients with major depression fail to respond satisfactorily to adequate first-line treatment. A frequent strategy for patients with insufficient response to an initial antidepressant dose is to increase the dose. This review is about this strategy, ie, the possible benefits of prescribing higher doses of recent antidepressants. The results show that a flat dose-response curve is a class phenomenon for selective serotonin reuptake inhibitors (SSRIs), according to randomized, controlled, fixed-dose clinical trials. For the serotonin and noradrenaline reuptake inhibitors (SNRIs), the strategy of dose increase may be relevant for venlafaxine, in order to increase the number of responders. Thus, the subgroup of patients for whom high doses of SSRIs could be useful remains to be defined.


Characterizing the grape transcriptome. Analysis of expressed sequence tags from multiple Vitis species and development of a compendium of gene expression during berry development.
We report the analysis and annotation of 146,075 expressed sequence tags from Vitis species. The majority of these sequences were derived from different cultivars of Vitis vinifera, comprising an estimated 25,746 unique contig and singleton sequences that survey transcription in various tissues and developmental stages and during biotic and abiotic stress. Putatively homologous proteins were identified for over 17,752 of the transcripts, with 1,962 transcripts further subdivided into one or more Gene Ontology categories. A simple structured vocabulary, with modules for plant genotype, plant development, and stress, was developed to describe the relationship between individual expressed sequence tags and cDNA libraries; the resulting vocabulary provides query terms to facilitate data mining within the context of a relational database. As a measure of the extent to which characterized metabolic pathways were encompassed by the data set, we searched for homologs of the enzymes leading from glycolysis, through the oxidative/nonoxidative pentose phosphate pathway, and into the general phenylpropanoid pathway. Homologs were identified for 65 of these 77 enzymes, with 86% of enzymatic steps represented by paralogous genes. Differentially expressed transcripts were identified by means of a stringent believability index cutoff of > or =98.4%. Correlation analysis and two-dimensional hierarchical clustering grouped these transcripts according to similarity of expression. In the broadest analysis, 665 differentially expressed transcripts were identified across 29 cDNA libraries, representing a range of developmental and stress conditions. The groupings revealed expected associations between plant developmental stages and tissue types, with the notable exception of abiotic stress treatments. A more focused analysis of flower and berry development identified 87 differentially expressed transcripts and provides the basis for a compendium that relates gene expression and annotation to previously characterized aspects of berry development and physiology. Comparison with published results for select genes, as well as correlation analysis between independent data sets, suggests that the inferred in silico patterns of expression are likely to be an accurate representation of transcript abundance for the conditions surveyed. Thus, the combined data set reveals the in silico expression patterns for hundreds of genes in V. vinifera, the majority of which have not been previously studied within this species.


Lionfish envenomations in an urban wilderness.
Marine envenomations are commonly encountered along coastal regions of the United States. Although less frequent, marine bites and stings do occur in landlocked locales, such as the Midwest, because of an increased interest in keeping these exotic creatures as pets. We report 33 cases of envenomations by captive lionfish (Pterois volitans) called to a regional Chicago poison control center over a 2-year period. All stings were accidental, and 10 (30%) were treated in an emergency department. The wounds were uniformly on the hand, and all presented with local, intense pain. The majority of envenomations were responsive to prompt immersion in nonscalding water within 90 min, and all were advised on tetanus prophylaxis and local wound care. Two patients (6%) required hospitalization. In all cases, those patients envenomated recovered without permanent sequelae. As a result of increasing encounters with lionfish as pets, health care providers. regardless of their locale, should be familiar with the current treatment recommendations.


Effects of fibronectin on the compact colony formation in staphylococci.
Fifty-two unencapsulated strains of Staphylococcus aureus, including strains of Wood 46 and Cowan I, formed compact colonies in fibronectin -soft agar. However, 20 encapsulated strains of Staphylococcus aureus and 50 strains of Staphylococcus epidermidis showed diffuse growth in the medium. The results suggest that another possible cellular factor, other than protein A, is involved in the binding of the cell surface with fibronectin and that it would be one of factors in forming compact colonies in serum-soft agar.


IFNG-mediated immune responses enhance autophagy against Mycobacterium tuberculosis antigens in patients with active tuberculosis.
Protective immunity against Mycobacterium tuberculosis (Mtb) requires IFNG. Besides, IFNG-mediated induction of autophagy suppresses survival of virulent Mtb in macrophage cell lines. We investigated the contribution of autophagy to the defense against Mtb antigen (Mtb-Ag) in cells from tuberculosis patients and healthy donors (HD). Patients were classified as high responders (HR) if their T cells produced significant IFNG against Mtb-Ag; and low responders (LR) when patients showed weak or no T cell responses to Mtb-Ag. The highest autophagy levels were detected in HD cells whereas the lowest quantities were observed in LR patients. Interestingly, upon Mtb-Ag stimulation, we detected a positive correlation between IFNG and MAP1LC3B-II/LC3-II levels. Actually, blockage of Mtb-Ag-induced IFNG markedly reduced autophagy in HR patients whereas addition of limited amounts of IFNG significantly increased autophagy in LR patients. Therefore, autophagy collaborates with human immune responses against Mtb in close association with specific IFNG secreted against the pathogen.