Update on pentamidine for the treatment of Pneumocystis carinii pneumonia.
The chemistry, spectrum of activity, mechanism of action, pharmacokinetics, adverse effects, and dosage and administration of pentamidine are reviewed, and the role of the drug in treating Pneumocystis carinii infections in immunocompromised patients is discussed. Pentamidine isethionate, an aromatic diamidine compound, is active against certain protozoan organisms. Used extensively in the tropics in the treatment of Trypanosoma and Leishmania infections, its value in the management of Pneumocystis carinii infections has been demonstrated in infected immunosuppressed children and adults. Recently, interest in pentamidine has increased with the rising number of patients with acquired immunodeficiency syndrome (AIDS) who have P. carinii pneumonia. Pentamidine's mechanism of action and pharmacokinetic profile are not completely understood. Pentamidine is distributed extensively after i.v. or i.m. administration, with a volume of distribution of 3 L/kg. Appreciable quantities of pentamidine concentrate in the urine, and drug levels are detectable for up to six to eight weeks after cessation of therapy. After aerosol administration, the drug is almost exclusively recovered from the lung, with little extrapulmonary distribution. Available data suggest that approximately 50% of patients who receive the drug by the i.v. or i.m. route will experience some drug toxicity (local pain, sterile abscesses at the intramuscular injection site, hypoglycemia, hypotension, or azotemia), while adverse effects after aerosol therapy include bronchial irritation but little systemic toxicity. Regardless of the route of administration, pentamidine has emerged as a mainstay of therapy in the management of P. carinii pneumonitis in AIDS patients, especially in those who are allergic to the sulfa component of trimethoprim-sulfamethoxazole.


The professional support group: a model for psychiatric clinical nurse specialists.
In addition to the frustrations experienced by any CNS, the psychiatric CNS in the general hospital setting experiences additional pressures which are inherent to his/her role. The major additional pressure is the great demand for the provision of support to patients, families, and staff. This necessitates a source of support for the psychiatric CNS. In response to this need, a group of psychiatric CNSs from general hospital settings developed and implemented a model for a professional support group. The formation and developmental process of this professional support group was consistent with literature descriptions of both small group and professional support group development. Informal evaluation demonstrated that this professional support group is achieving its purposes, and continues to function as an ongoing group.


Kinetics of protein aggregation. Quantitative estimation of the chaperone-like activity in test-systems based on suppression of protein aggregation.
The experimental data on the kinetics of irreversible aggregation of proteins caused by exposure to elevated temperatures or the action of denaturing agents (guanidine hydrochloride, urea) have been analyzed. It was shown that the terminal phase of aggregation followed, as a rule, first order kinetics. For the kinetic curves registered by an increase in the apparent absorbance (A) in time (t) the methods of estimation of the corresponding kinetic parameters A(lim) and kI (A(lim) is the limiting value of A at t --> infinity and kI is the rate constant of the first order) have been proposed. Cases are revealed when the reaction rate constant kI calculated from the kinetic curve of aggregation of the enzymes coincides with the rate constant for enzyme inactivation. Such a situation is interpreted as a case when the rate of aggregation is limited by the stage of denaturation of the enzyme. A conclusion has been made that, in order to establish the mechanism of protein aggregation, the kinetic investigations of aggregation should be carried out over a wide range of protein concentrations. The refolding experiments after denaturation of proteins by guanidine hydrochloride or urea have been also analyzed. It was shown that aggregation accompanying refolding follows first order kinetics at the final phase of the process. The model of protein refolding explaining such a kinetic regularity has been proposed. When aggregation of protein substrate follows first order kinetics, parameters A(lim) and kI may be used for the quantitative characterization of the chaperone-like activity in the test-systems based on suppression of protein aggregation.


Role of folate receptor genes in reproduction and related cancers.
The expression patterns of folate receptor (FR) isoforms, alpha and beta, in normal and malignant male and female reproductive tissues is described. The significance of the receptor in reproductive and developmental physiology is discussed. The potential value of the receptor expressed in malignant tissues including ovarian and endometrial cancers as a diagnostic marker and a therapeutic target is reviewed. Finally, the various transcriptional and post-transcriptional mechanisms that govern the tissue/tumor-specificity of the receptor and its regulation by folate and steroid receptor ligands are described; the potential value of this knowledge in developing better methods for the early detection and treatment of certain cancers is discussed.


Separation of experimental 2D IR frequency-frequency correlation functions into structural and reorientation-induced contributions.
A vibrational transition frequency can couple to its environment through a directional vector interaction. In such cases, reorientation of the vibrational transition dipole (molecular orientational relaxation) and its frequency fluctuations can be strongly coupled. It was recently shown [Kramer et al., J. Chem. Phys. 142, 184505 (2015)] that differing frequency-frequency correlation function (FFCF) decays, due to reorientation-induced spectral diffusion (RISD), are observed with different two-dimensional infrared polarization configurations when such strong coupling is present. The FFC functional forms were derived for the situation in which all spectral diffusion is due to reorientational motion. We extend the previous theory to include vibrational frequency evolution (spectral diffusion) caused by structural fluctuations of the medium. Model systems with diffusive reorientation and several regimes of structural spectral diffusion rates are analyzed for first order Stark effect interactions. Additionally, the transition dipole reorientational motion in complex environments is frequently not completely diffusive. Several periods of restricted angular motion (wobbling-in-a-cone) may precede the final diffusive orientational randomization. The polarization-weighted FFCF decays are presented in this case of restricted transition dipole wobbling. With these extensions to the polarization-dependent FFCF expressions, the structural spectral diffusion dynamics of methanol in the room temperature ionic liquid 1-hexyl-3-methylimidazolium hexafluorophosphate can be separated quantitatively from RISD using the experimental center line slope data. In addition, prior results on the spectral diffusion of water, methanol, and ethanol in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide are re-examined to elucidate the influence of reorientation on the data, which were interpreted in terms of structural fluctuations.


COVID-19-We urgently need to start developing an exit strategy.
The purpose of this perspective is to review the options countries have to exit the draconian "lockdowns" in a carefully staged manner. Experts from different countries experiencing Corona Virus Infectious Disease 2019 (COVID-19) reviewed evidence and country-specific approaches and the results of their interventions. Three factors are essential: 1. Reintroduction from countries with ongoing community transmission; 2. The need for extensive testing capacity and widespread community testing, and 3. An adequate supply of personal protective equipment, PPE, to protect health care workers. Discussed at length are lifting physical distancing, how to open manufacturing and construction, logistics, and the opening of higher educational institutions and schools. The use of electronic surveillance is considered. Each country should decide on the best path forward. However, we can learn from each other, and the approaches are, in reality, very similar.


Charcot foot.
Charcot joint is the painless, degenerative, progressive neuropathic destruction of the bony architecture of one or more joints of the feet. Diabetes mellitus is the most common cause of Charcot joint in North America, although the exact etiology is uncertain. The classic presenting complaint involves unilateral painless swelling of the lower extremity or foot. Charcot joint is often mistaken for cellulitis or deep vein thrombosis and may result in significant foot or ankle deformities. There are several treatment options for the patient presenting with Charcot joint. Medical management often includes immobilization and maintaining nonweightbearing status. Surgical intervention, often a final attempt at managing Charcot foot, involves careful patient selection and is not recommended for all patients. The postoperative phase can be challenging for both patient, nursing staff, and the surgeon.


Microbial biofilm community structure and composition on the lithic substrates of Herculaneum Suburban Baths.
In this work, we want to investigate the impact of different substrates and different environmental condition on the biofilm communities growing on plaster, marble, and mortar substrates inside the Herculaneum Suburban Baths. To do so, we measured environmental conditions and sampled biofilm communities along the walls of the baths and used culture-dependent and -independent molecular techniques (DGGE) to identify the species at each sampling sites. We used the species pool to infer structure and richness of communities within each site in each substrate, and confocal light scanning microscopy to assess the three-dimensional structure of the sampled biofilms. To gather further insights, we built a meta-community network and used its local realizations to analyze co-occurrence patterns of species. We found that light is a limiting factor in the baths environment, that moving along sites equals moving along an irradiation gradient, and that such gradient shapes the community structure, de facto separating a dark community, rich in Bacteria, Fungi and cyanobacteria, from two dim communities, rich in Chlorophyta. Almost all sites are dominated by photoautotrophs, with Fungi and Bacteria relegated to the role of rare species., and structural properties of biofilms are not consistent within the same substrate. We conclude that the Herculaneum suburban baths are an environment-shaped community, where one dark community (plaster) and one dim community (mortar) provides species to a "midway" community (marble).


Alopecia Induced by Autologous Fat Injection into the Temporal Area: Case Report and Review of the Literature.
Alopecia secondary to facial filler injections is a highly unusual sequela. Only 2 cases of hyaluronic acid-induced alopecia have been reported to date. Accumulating evidence suggests vascular compromise as its etiology, which can be accidental intravascular injection or external compression by overfilled materials. We hereby present, to the best of our knowledge, the first case of localized nonscarring and scarring alopecia secondary to autologous fat grafting and review the literature regarding filler-induced alopecia.


Review of chemotherapy-associated paronychia.
Chemotherapy-associated paronychia (CAP) is an inflammation of the nail folds in response to various chemotherapeutic medications. Altered proliferation of keratinocytes or nail matrix stem cells is thought to be a major causative factor. Prophylactic tetracyclines, topical povidone-iodine, and general irritation avoidance measures are among some of the recommended interventions for CAP. Appropriate recognition and treatment of CAP are important for prevention of chemotherapy dose reduction or medication discontinuation.


[Current status of use of the artificial heart in combination with heart transplantation].
Acute and therapeutically uncontrollable cardiac insufficiency in a case of chronic heart disease with acute risk of rejection and with a record of previous transplantation or during a heart operation should be considered as an indication for implantation of an artificial heart or a ventricle-supporting system, if a donor heart is not available. Two results are expected from such an approach, restoration of adequate circulation and improvement of organ functionally providing a chance for later transplantation. Attention should be given, according to the authors' own experience, to effective surgical haemostasis. Infections have quite often proved to be incurable after implantation of an artificial heart and, consequently, provide a clear-cut contraindication to implantation.


Neonatal lupus in twins.
Neonatal lupus erythematosus (NLE) is a syndrome characterized by one or all of the following elements: cutaneous LE lesions, systemic disease, and congenital heart block. SS-A/Ro and SS-B/La have been implicated in the etiology of NLE, but because NLE is not uniformly manifested in all offspring of SS-A and SS-B autoantibody positive mothers, and because of the wide range of clinical manifestations associated with NLE, other contributing etiologic factors are being explored. HLA studies have revealed that infants of SS-A/Ro and SS-B/La positive mothers bearing HLA-A1, B8, DR3, DQ2, and DR52 are at greater risk of having NLE. Haplotyping in our dizygous twins supports these material HLA associations.


[Fractures of the tibia's intercondylar eminentia in children].
We have described management in tibia's intercondylar eminentia fractures in children, based on own data and review of the contemporary bibliography. The data contain 16 children from 6 to 14 years of age with all Meyers' and McKeever' fractures types. Type I and II fractures can be treated conservatively. Such factors like fracture's type and child's age must be taken under consideration for an operative treatment most often, but in children below 10 years of age, the conservative one should be considered as well.


The mechanism of flutter interval alternans.
The mechanism of atrial flutter alternans was investigated by observing the effects of ventricular systole on flutter intervals in a patient with atrioventricular dissociation. Interval measurements were made both from atrial electrograms recorded from an esophageal electrode, and from surface ECG recordings. Flutter cycle intervals that occurred during a well-defined period subsequent to ventricular systole were consistently prolonged by up to 30 msec relative to the baseline flutter cycle interval. This prolongation was observed in two vastly different electrode configurations, implying that motion artifact was not predominantly responsible. We concluded that, by altering the characteristics of the flutter reentry circuit, transient increases in atrial volume and/or pressure arising during ventricular systole were responsible for the lengthening of the flutter cycle intervals.


Dietary patterns associated with vitamin/mineral supplement use and smoking among women of the E3N-EPIC cohort.
An understanding of the relationships between dietary habits and supplement use or smoking is useful for aetiological studies and surveillance purposes. The objective of this study is to describe dietary patterns associated with vitamin/mineral supplement use and smoking habits in French women. Scores for dietary patterns were obtained by factor analysis in 64,252 women from the French E3N-EPIC cohort. The association with supplement and tobacco use was investigated by logistic regression analysis. We identified three dietary patterns: 'processed meat/starchy foods' (fast foods, processed meat, rice/pasta/semolina and cakes and few vegetables); 'fruit/vegetables' (fruits, vegetables, seafood, vegetable oils and yoghurt); and 'alcohol/meat products' (alcohol, meat and meat products, and coffee, and few fruits and soup). Supplement use was positively associated with the fruit/vegetables pattern (multivariate OR for quartile 4 versus 1 (OR(4))=1.55, 95% confidence interval: 1.47-1.63), and inversely associated with the processed meat/starchy foods (OR(4)=0.84; 0.80-0.89) and alcohol/meat products (OR(4)=0.69; 0.66-0.73) patterns (P trend for all associations <0.0001). As compared with never smoking, current smoking was inversely associated with the fruit/vegetables pattern (OR(4)=0.85; 0.78-0.92), while former smoking was positively associated with the fruit/vegetables pattern (OR(4)=1.32; 1.25-1.40); both current and former smoking were inversely associated with the processed meat/starchy foods pattern (OR(4)=0.57; 0.53-0.62 and 0.64; 0.60-0.67, respectively); whereas current and former smoking were both strongly positively associated with the alcohol/meat products pattern (OR(4)=5.78; 5.26-6.36 and 2.03; 1.91-2.15, respectively); P trend for all associations was <0.001. Supplement use and smoking are strongly associated with dietary patterns.


Chromosome congression by Kinesin-5 motor-mediated disassembly of longer kinetochore microtubules.
During mitosis, sister chromatids congress to the spindle equator and are subsequently segregated via attachment to dynamic kinetochore microtubule (kMT) plus ends. A major question is how kMT plus-end assembly is spatially regulated to achieve chromosome congression. Here we find in budding yeast that the widely conserved kinesin-5 sliding motor proteins, Cin8p and Kip1p, mediate chromosome congression by suppressing kMT plus-end assembly of longer kMTs. Of the two, Cin8p is the major effector and its activity requires a functional motor domain. In contrast, the depolymerizing kinesin-8 motor Kip3p plays a minor role in spatial regulation of yeast kMT assembly. Our analysis identified a model where kinesin-5 motors bind to kMTs, move to kMT plus ends, and upon arrival at a growing plus end promote net kMT plus-end disassembly. In conclusion, we find that length-dependent control of net kMT assembly by kinesin-5 motors yields a simple and stable self-organizing mechanism for chromosome congression.


Reconstruction of traumatic orbital floor defects using irradiated cartilage homografts.
The important role of orbital shape and volume reconstruction has been studied by many investigators. There is, however, no consensus on the material that should be used in the reconstruction of the orbit. Both biologic and alloplastic materials have been used, each with its advantages and disadvantages. Here we report our experience with irradiated costal cartilage homograft in the reconstruction of the orbital floor. Irradiated cartilage grafts were used in 31 patients with significant traumatic defects in the orbital floor. Long-term follow-up in 21 patients up to 48 months revealed no incidence of graft infections, extrusions, or clinically detectable graft distortion or resorption. Irradiated cartilage homograft appears to be an excellent material for reconstruction of the orbital floor.


Long-term regulation of leptin expression is correlated with adipocyte number in obese rats.
To investigate long-term regulation of leptin expression in adipose tissues of obese JCR:LA-corpulent rats, which have been shown to overexpress leptin. Manipulation of adipose tissue growth in obese rats by dietary restriction. Weanling female obese rats were maintained on 1 of 3 diets until 8 months old. One group was allowed to feed ad libitum, the second was pair-fed with lean rats, and the third had food intake restricted to maintain weights equal to those of age-matched lean rats. Body and fat pad weights, leptin messenger RNA (mRNA) levels, and size and number of adipocytes in retroperitoneal fat pads. Adipose tissue mass was increased 6-fold in the obese rats compared with the lean ones, despite equal body weight and intake restriction that was sufficient to impair growth. Although leptin mRNA level was down-regulated by intake restriction, it was still twice as elevated in the obese rats as in the lean ones, and was highly correlated with specific fat pad mass and adipocyte number, but not with size. These data suggest that leptin expression is correlated with adipocyte number within a fat pad, and that there is inappropriate hepatic de novo synthesis and storage of triacylglycerols in obese rats. A role for leptin in nutrient partitioning is proposed.


Anti-NMDAR Encephalitis Following Herpes Simplex Virus Encephalitis: 2 Cases From Portugal.
Herpes simplex virus encephalitis (HSVE) usually presents as a monophasic disease. Symptomatic HSVE relapsing with seizures, encephalopathy, or involuntary movements associated with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis have been recently reported. We report 2 cases of adult post-HSVE anti-NMDAR encephalitis from Portugal. Two female patients aged 50 years and 30 years were diagnosed with herpes simplex virus type 2 and type 1 encephalitis, respectively. After the initial improvement with specific treatment and despite virologic negativization, both patients suffered clinical, electroencephalographic, and imaging deterioration. The autoimmune encephalitis hypothesis was confirmed with the demonstration of anti-NMDAR antibodies in both cerebrospinal fluid and serum. Both responded to human immunoglobulin and methylprednisolone, with progressive gain of autonomy along the follow-up period. Thymectomy for thymic hyperplasia diagnosed during follow-up was performed in 1 patient. Although being rare, post-HSVE anti-NMDAR encephalitis should be considered in all cases of symptomatic recrudescence after HSVE, since adequate immune-modulating treatment improves the outcome. The role of thyme hyperplasia in autoimmune encephalitis pathogenesis needs better understanding.


Influence of placement depth and abutment connection pattern on bone remodeling around 1-stage implants: a prospective randomized controlled clinical trial.
The aim of this study is to evaluate peri-implant marginal bone level changes in relation to crestal or subcrestal implant placement and type of fixture/abutment connection 3 months after implant placement. The duration of the study was 3 months. A total of 105 implants were placed in 81 subjects following a one-stage surgical procedure and assigned into four groups. In the first and second groups, implants with a screwed tapered internal connection were placed subcrestally and crestally, respectively, while in the third and fourth groups, implants with an internal conical seal connection were similarly placed. Clinical recordings and standardized periapical digital radiographs were taken the day of implantation and 3 months later, before placement of the final prosthetic restoration. The modified plaque index (mPLI), modified gingival index (mGI), and probing depths (PD) were recorded at four sites around each implant, and the vertical distance between fixture/abutment junction and alveolar crest at the mesial and distal sites of each implant utilizing subtractive radiography were all measured on placement and at 3 months. There was no statistically significant difference between the four groups for PD. The highest values of mPLI and mGI were recorded for Group 2. The mean (±SE) peri-implant bone loss was recorded as follows: Group 1: 0.68 ± 0.07 mm, Group 2: 0.79 ± 0.06 mm, Group 3: 0.49 ± 0.06 mm, and Group 4: 0.40 ± 0.07 mm. The statistical analysis revealed significant differences in bone resorption between groups with different abutment connections. The connection between fixture/abutment rather than vertical implant placement in relation to alveolar bone level seems to affect peri-implant marginal bone resorption.


Using a Patient Safety/Quality Improvement Model to Assess Telehealth for Psychiatry and Behavioral Health Services Among Special Populations During COVID-19 and Beyond.
Telehealth has been rapidly deployed in the environment of the Coronavirus 2019 (COVID-19) pandemic to help meet critical mental health needs. As systems of care use telehealth during the pandemic and evaluate the future of telehealth services beyond the crisis, a quality and safety framework may be useful in weighing important considerations for using telehealth to provide psychiatric and behavioral health services within special populations. Examining access to care, privacy, diversity, inclusivity, and sustainability of telehealth to meet behavioral and psychiatric care needs in geriatric and disadvantaged youth populations can help highlight key considerations for health care organizations in an increasingly electronic health care landscape.


High etendue UV camera for simultaneous four-color imaging on a single detector.
We describe a high etendue (0.12 cm(2) sr) camera that, without moving parts, simultaneously images four ultraviolet bands centered at 140, 175, 215, and 255 nm on a single detector into a minimum of ~7500 resolution elements. In addition to being an efficient way to make color photometric measurements of a static scene, the camera described here enables detection of spatial and temporal information that can be used to reveal energy dependent physical phenomena to complement the capability of other instruments ranging in complexity from filter wheels to integral field spectrographs.


Development of tyrosine hydroxylase-like immunoreactive structures in the chick retina: three-dimensional analysis.
This study was designed to investigate the developmental profile of tyrosine hydroxylase-like immunoreactive structures in the chick retina in both frozen sections and wholemount preparations. In frozen sections, cells with tyrosine hydroxylase-like immunoreactivity were first detected in 10 to 15 cell rows from the innermost part of the inner nuclear layer on embryonic or incubation day 11. They were seen in the inner cell rows of the inner nuclear layer during later periods; by embryonic day 18, the immunoreactive cells were located 1 to 3 cell rows outward from the innermost part of the inner nuclear layer where mature immunoreactive cells mainly exist. The immunoreactive cells began to give rise to processes on embryonic day 13. The processes (possibly dendrites) gradually increased in number and intensity in sublayers 1 and 4 of the inner plexiform layer during prenatal life. Several days after hatching, an abrupt increase in immunoreactive processes was noted in sublayer 1 but not in sublayer 4. On the sixth postnatal day, retinal neural elements immunoreactive for tyrosine hydroxylase seemed to exhibit a distribution pattern similar to that of the adult chick. In wholemount retinas, immunoreactive cells were initially detected at the earliest stage of embryonic day 12 in a small circle termed "starting area" occupying the ventral part of the temporal retinal field. The closer to the "starting area," the earlier the retinal area began to express many immunoreactive cells. Thus tyrosine hydroxylase cell density in individual retinal areas, as represented by cell number per square millimeter, peaked in different developmental periods varying from embryonic day 12 to day 14. At this stage, immunoreactive cells were arranged irregularly in the retina. Thereafter, the cell density as well as total cell number gradually declined and reached a plateau around embryonic day 20 when tyrosine hydroxylase-like immunoreactive cells, like those in the mature retina, showed an even distribution throughout the retina.(ABSTRACT TRUNCATED AT 400 WORDS)


Evidence-based optimal fluconazole dosing regimen for onychomycosis treatment.
Fluconazole could be an alternative to terbinafine and itraconazole for onychomycosis treatment. However, it is difficult to determine the optimal dosing regimen due to the variability in causative agents, dosing regimens and cure rates in clinical trials. By restricting the data to dermatophyte onychomycosis, we aimed to identify an optimal fluconazole dosing regimen. We searched the PubMed, EMBASE and CENTRAL databases and the reference sections of published literature for clinical trials on fluconazole monotherapy for culture-proven dermatophyte onychomycosis. Relationships between fluconazole doses, cure rates and duration of therapy were analyzed. Longer treatments, but not higher weekly fluconazole doses, resulted in better cure rates for toenail, and possibly fingernail, onychomycosis. Consequently, mean mycological and clinical cure rates for treatments lasting 6 months or less and more than 6 months were significantly different for toenail onychomycosis. Clinical studies including participants with nondermatophyte mold, Candida species, or negative culture onychomycosis only used fluconazole therapy for 6 months or less. Thus, the relationship between cure rates and duration of treatment could not be confirmed for all causative agents. The lowest dose of 150 mg weekly for more than 6 months is recommended for onychomycosis.


Basic fibroblast growth factor stimulates activation of Rac1 through a p85 betaPIX phosphorylation-dependent pathway.
In a previous study (Shin, E. Y., Shin, K. S., Lee, C. S., Woo, K. N., Quan, S. H., Soung, N. K., Kim, Y. G., Cha, C. I., Kim, S. R., Park, D., Bokoch, G. M., and Kim, E. G. (2002) J. Biol. Chem. 277, 44417-44430) we reported that phosphorylation of p85 betaPIX, a guanine nucleotide exchange factor (GEF) for Rac1/Cdc42, is a signal for translocation of the PIX complex to neuronal growth cones and is associated with basic fibroblast growth factor (bFGF)-induced neurite outgrowth. However, the issue of whether p85 betaPIX phosphorylation affects GEF activity on Rac1/Cdc42 is yet to be explored. Here we show that Rac1 activation occurs in a p85 betaPIX phosphorylation-dependent manner. A GST-PBD binding assay reveals that Rac1 is activated in a dose- and time-dependent manner in PC12 cells in response to bFGF. Inhibition of ERK or PAK2, the kinases upstream of p85 betaPIX in the bFGF signaling, prevents Rac1 activation, suggesting that phosphorylation of p85 betaPIX functions upstream of Rac1 activation. To directly address this issue, transfection studies with wild-type and mutant p85 betaPIX (S525A/T526A, a non-phosphorylatable form) were performed. Expression of mutant PIX markedly inhibits both bFGF- and nerve growth factor (NGF)-induced activation of Rac1, indicating that phosphorylation of p85 betaPIX is responsible for activation of this G protein. Both wild-type and mutant p85 betaPIX displaying negative GEF activity (L238R/L239S) are similarly recruited to growth cones, suggesting that Rac1 activation is not essential for translocation of the PIX complex (PAK2-p85 betaPIX-Rac1). However, expression of mutant p85 betaPIX (L238R/L239S) results in retraction of the pre-existing neurites. Our results provide evidence that bFGF- and NGF-induced phosphorylation of p85 betaPIX mediates Rac1 activation, which in turn regulates cytoskeletal reorganization at growth cones, but not translocation of the PIX complex.


The Noc region of Ti plasmid C58 codes for arginase and ornithine cyclodeaminase.
Plant tumors induced by Agrobacterium tumefaciens synthesize a group of substances (opines) which can serve as sole source of carbon and nitrogen for the bacteria. We investigate Ti-plasmid-coded genes and enzymes involved in catabolism of the opine N2-(1,3-dicarboxypropyl)-L-arginine (nopaline) with a novel approach: expression and mapping of protein-coding regions in Escherichia coli minicells, followed by identification of enzyme functions in the heterologous E. coli background. The results show that a specific part of the nopaline catabolism (Noc) region of Ti plasmid C58 is packed with closely spaced protein-coding regions which can be expressed into polypeptides of distinct sizes in E. coli. We identify and map three enzyme activities: nopaline oxidase, arginase and ornithine cyclodeaminase, an unusual protein converting ornithine directly into proline. Nopaline oxidase requires two different Noc-gene-encoded proteins for function and the latter two enzymes are new discoveries in the Noc region. These three enzyme activities together constitute a catabolic pathway leading from nopaline through arginine and ornithine to proline.


Folliculosebaceous neoplasms: A review of clinical and histological features.
Numerous benign and occasionally malignant tumors arise from the folliculosebaceous apparatus. Confusing terminology, rarity of malignant variants and overlapping histological features can lead to diagnostic uncertainty. This review highlights the clinical and histopathological features that help to classify these entities, as well as the various syndromes associated with certain members of this large family of tumors.


A systematic review of historical and current trends in Chagas disease.
Chagas disease (CD) is caused by Trypanosoma cruzi. When acquired, the disease develops in stages. For diagnosis, laboratory confirmation is required, and an extensive assessment of the patient's health should be performed. Treatment consists of the administration of trypanocidal drugs, which may cause severe adverse effects. The objective of our systematic review was to analyze data contained in the CD published case reports to understand the challenges that patients and clinicians face worldwide. We performed a systematic review following the PRISMA guidance. PubMed database was explored using the terms 'American trypanosomiasis' or 'Chagas disease'. Results were limited to human case reports written in English or Spanish. A total of 258 reports (322 patients) were included in the analysis. Metadata was obtained from each article. Following this, it was analyzed to obtain descriptive measures. From the sample, 56.2% were males and 43.8% were females. Most cases were from endemic countries (85.4%). The most common clinical manifestations were fever during the acute stage (70.0%), dyspnea during the chronic stage in its cardiac form (53.7%), and constipation during the chronic stage in its digestive form (73.7%). Most patients were diagnosed in the chronic stage (72.0%). Treatment was administered in 56.2% of cases. The mortality rate for the acute stage cases was 24.4%, while for the chronic stage this was 28.4%. CD is a parasitic disease endemic to Latin America, with increasing importance due to human and vector migration. In this review, we report reasons for delays in diagnosis and treatment, and trends in medical practices. Community awareness must be increased to improve CD's diagnoses; health professionals should be appropriately trained to detect and treat infected individuals. Furthermore, public health policies are needed to increase the availability of screening and diagnostic tools, trypanocidal drugs, and, eventually, vaccines.


Noncoordinated expression of S6, S11, and S14 ribosomal protein genes in leukemic blast cells.
The steady state levels of mRNAs codying for the ribosomal proteins S6, S11, and S14 have been evaluated in quiescent and proliferating human fibroblasts and in resting and proliferating human peripheral blood mononuclear cells. It was found that the amounts of ribosomal protein mRNA are very similar and are not increased by serum or mitogen stimulation. The constitutive expression of these genes appears to be coordinately regulated and it is not modified after protein synthesis inhibition by cycloheximide. The ribosomal protein mRNA was also assayed in 15 different populations of human leukemic blast cells. In these populations the abundance of each ribosomal protein mRNA is remarkably different from the other. The results of our present experiments indicate that the expression of the three ribosomal protein genes undergoes independent noncoordinated changes in the large majority of the leukemic populations studied.


Analyzing Survival Rate of Leukemia Patients Applying Long Term Exponential Model.
Making progressin treatment of all branches of cancers has increasedthe percent of patients that never experience the event of interest. These cases are called immune or cure and models for handling the data included cure fraction rate, are referred to as cure model or long-term survival models. The data for this historical cohort study, were collected from leukemia patients diagnosed between 2007 to 2014 and followed up until 2016 in Taleghani hospital and received BMT (Bone Marrow Transplant). Some data had to be excluded because of incomplete information. Using recorded files mostly and phone calls rarely, were made to confirm whether the patients were still alive or not. Death due to leukemia was regarded as interested event. Analysis were performed by R version 3.4.1and Stata version 14. Number of recurrents after receiving BMT, pre-transplant Hb and age at diagnosis were found as significant prognostics of survival time. HD patients had the highest 5-years overall survival in category of diagnosis type with 81.3%. Cure fraction was estimated to be 64.1%. According to high percentage of censoring, using long-term model had better fit.


Progress towards the development of Klebsiella vaccines.
Introduction: Klebsiella pneumoniae (KP) are a leading cause of healthcare-associated infections. The dramatic increase in microbial resistance to third-generation cephalosporin and carbapenem 'front line' antimicrobial agents and the paucity of new antimicrobials have left clinicians with few therapeutic options and resulted in increased morbidity and mortality. Vaccines may reduce the incidence of infections thereby reducing the necessity for antimicrobials and are not subject to antimicrobial resistance mechanisms. Areas covered: We review whole cell, subunit, capsular polysaccharide (CPS), O polysaccharide (OPS) and conjugate vaccines against KP infection, as well as alternative KP vaccine platforms. Expert opinion: Vaccine-induced antibodies to KP CPS have been protective in preclinical studies, but the number of CPS types (>77) makes vaccines against this virulence factor less feasible. Since four OPS serotypes account of ~80% of invasive KP infections and anti-OPS antibodies are also protective in preclinical studies, both OPS-based conjugate and multiple antigen presenting system (MAPS) vaccines are in active development. Vaccines based on other KP virulence factors, such as outer membrane proteins, type 3 fimbriae (MrkA) and siderophores are at earlier stages of development. Novel strategies for the clinical testing of KP vaccines need to be developed.


Detection of rifampin resistance among isolates of Mycobacterium tuberculosis from Mozambique.
Rifampin resistance in respiratory isolates of Mycobacterium tuberculosis from Mozambique was detected by screening for point mutations using polymerase chain reaction (PCR) and DNA sequence analysis. The target template was a 350-bp fragment of rpoB encoding the beta-subunit of the RNA polymerase. Of the 66 strains studied, 38 were rifampin resistant by susceptibility testing with the radiometric method, 3 were intermediately resistant, and 25 were susceptible to rifampin. In 39 of the 41 rifampin-resistant strains, base-substitutions in the rpoB fragment were detected, and a total of 13 distinct mutations affecting 6 amino acids were observed. One of these mutations (His-->Thr in amino acid 526) was not previously described. The isolates were also investigated by restriction fragment length polymorphism (RFLP) analysis using the insertion element IS6110 as a hybridization probe. A total of 47 RFLP patterns were identified, with up to 9 isolates having the same RFLP pattern. Strains with the same RFLP pattern harbored different mutations in rpoB, suggesting that acquisition of rifampin resistance followed the spread of a rifampin-susceptible clone. The data showed that rifampin resistance can be detected with a high sensitivity by DNA sequence analysis of this fragment of rpoB. However, a few strains with rifampin resistance due to factors other than base substitutions in rpoB could be missed.


Prevalence and diagnostic accuracy of Doppler ultrasound of placenta accreta in Egypt.
The objective of this study is to assess the prevalence of placenta accrete (PA) among those with placenta implanted over cesarean section (CS) scar and to evaluate the accuracy of Doppler ultrasound in diagnosis. A cross-sectional study included 100 patients with placenta previa (PP) anterior with at least one previous CS. Ultrasound and color Doppler were done to all participants and correlated with operative findings. There was a significant difference between accrete and non-accrete group regarding maternal age (32.6 ± 5.01 versus 29.14 ± 4.89), and a highly significant difference regarding the postoperative hemoglobin (6.71 ± 1.156 versus 8.41 ± 1.257) and the number of previous CSs (p <.001). The abnormal Doppler findings showed a highly significant difference between the two groups as loss of retroplacental clear zone (87.3% versus 10.8%), intraplacental lacunae (93.7% versus 37.8%), hypervascularity in uterine bladder interface (47.6% versus 5.4%), and blood vessels invading myometrium (82.5% versus 18.9%) (p < .001). The sensitivity, specificity, PPV, NPV, and accuracy of loss of retroplacental clear were 87.3%, 89.19%, 93.2%, 80.49%, and 88%; intraplacental lacunae were 93.65%, 62.16%, 80.82%, 85.19%, and 82%; hypervascularity in uterine bladder interface were 47.62%, 94.59%, 93.75%, 51.47%, and 65%; dilated vessels over peripheral subplacental zone were 82.54%, 81.08%, 88.14%, 73.17%, and 82%, respectively. There was a highly significant difference between the two groups regarding surgical management with cesarean hysterectomy, occurrence of bladder injury, the need for intraoperative, and postoperative blood transfusion, ICU admission (p < .001). The use of ultrasound together with the color Doppler allowed for better prediction of placental invasion of the myometrium prior to obstetrical intervention to improve the maternal and the fetal outcome.


Psychological Distress, Anxiety, Family Violence, Suicidality, and Wellbeing in Pakistan During the COVID-19 Lockdown: A Cross-Sectional Study.
The purpose of this study was to draw the attention toward the implications of COVID-19 and the related restrictions imposed worldwide especially in Pakistan. The primary objective was to highlight the levels of psychological distress, anxiety, family violence, suicidality, and well-being due to COVID-19 and the secondary objective was to associate it to social demographic factors. It is designed as a cross-sectional study by employing an online questionnaire in the English language and obtaining responses using a snowball sampling technique. We used three validated measures including Kessler Psychological Distress Scale (K10), Generalized Anxiety Disorder (GAD-7) index and World Health Organization Well-Being Index (WHO-5). A sample of 420 participants was recruited from across Pakistan, with most participants were females (79%), students (89.8%) and belonging to Punjab (54%). Nearly one-fourth of the participants (23.8%) scored above the minimum value set for moderate or high psychological distress (K10 > 12). There was a higher prevalence of distress among females and resident of province Punjab. The majority of individuals reported that they were living with their family (94.5%) and more than half (52.6%) were neutral regarding their satisfaction with their living conditions. 40.5% believed that the lockdown has had a negative impact on their mental health. 31.4% have reported that they themselves have experienced abuse from a family member. 48.6% scored high on the GAD-7 scale and low wellbeing score was found among 80.2%. Students were found to be more vulnerable to mental illness and anxiety. With the lockdown restrictions, psychosocial distress has become prevalent in Pakistan.


Controlling the morphology of copolymeric vectors for next generation nanomedicine.
Amidst the wealth of information that the past few decades of nanomedical research has given us there is one design principle that has emerged as being key for the success of delivery vectors: particle morphology. This review seeks to unpack the various facets of particle morphology that are important for effective integration in vivo. In order to understand the contribution of morphology towards the biophysical function of nanovectors it is important to consider the historical development of such systems and how their physicochemical characteristics are selected. Ultimately, the purpose of this review is to give a clear perspective for the development of future nanovectors and how an integrated approach to their design, with particular focus upon their morphological features (size, shape, stimuli-responsiveness and surface chemistry), is vital for their performance in vitro and in vivo.


Cone arthrodesis of the first metatarsophalangeal joint.
The reliability and effectiveness of the treatment of hallux rigidus and symptomatic arthritis of the first metatarsophalangeal joint by the technique of cone arthrodesis are discussed. The authors reviewed the long-term results of cone arthrodesis in 51 patients with 60 operated feet. The average age was 55 years (range, 28 to 75 years) and the average length of follow-up was 39 months (range, 1 to 12 years). On questioning the patients regarding function, cosmesis, and pain, 41 of 51 patients were happy, eight of 51 patients were satisfied, and two of 51 were unhappy with their feet. No patient complained of persistent or recurrent hallux valgus deformity. Radiologically and clinically 58 of 60 first metatarsophalangeal joints were solidly fused. Two patients had a fibrous ankylosis which was functional and painless. Function with respect to gait and ability to walk on tiptoe and run was normal in all patients. In summary, the authors feel that this procedure is a reliable, effective treatment of painful arthritis of this joint.


Development of sheath-flow probe electrospray ionization mass spectrometry and its application to real time pesticide analysis.
For the real time and direct analysis of chemical constituents from living beings and dry sample, sheath-flow probe electrospray ionization mass spectrometry (SF-PESI-MS) has been newly developed. The components from dry or semidry biological tissues can be extracted using the solvent and picked up by the needle for electrospray. This technique was applied to real-time pesticide analysis of living plants. The results have been validated with that of a well-known system, liquid extraction surface analysis mass spectrometry (LESA-MS). It is demonstrated that SF-PESI-MS can produce reasonable ionization efficiency, which is confirmed by LESA-MS.


Iron Overload in Survivors of Childhood Cancer.
Iron overload is a significant cause of morbidity and mortality for patients who require frequent transfusions. We completed a prospective, cross-sectional study to evaluate the prevalence of iron overload in previously transfused childhood cancer survivors. Survivors recruited from the University of Minnesota Long-Term Follow-Up Clinic were stratified into 3 groups: oncology patients not treated with hematopoietic stem cell transplantation (HSCT) (n=27), patients treated with allogeneic HSCT (n=27), and patients treated with autologous HSCT (n=9). Serum ferritin was collected and hepatic magnetic resonance imaging (FerriScan) was obtained for those with iron overload (defined as ferritin ≥1000 ng/mL). The prevalence of iron overload in subjects with a history of allogeneic HSCT was 25.9% (95% CI, 9.4%-42.5%) compared with only 3.7% (95% CI, 0%-10.8%) in subjects treated without HSCT and 0% in subjects treated with autologous HSCT. No association was found between serum ferritin levels and the presence of cardiac, liver, or endocrine dysfunction. The prevalence of iron overload in subjects who received no HSCT or autologous HSCT is low in our study. A higher prevalence was found in patients receiving allogeneic HSCT, reiterating the importance of screening these patients for iron overload in accordance with the current Children's Oncology Group Long Term Follow-Up Guidelines.


A nonneutralizing anti-HIV Type 1 antibody turns into a broad neutralizing antibody when expressed on the surface of HIV type 1-susceptible cells. II. Inhibition of HIV type 1 captured and transferred by DC-SIGN.
Previously, we demonstrated that the expression of a nonneutralizing human anti-HIV-1 gp41 scFv on the surface of HIV-1-susceptible cells markedly inhibits HIV-1 replication and HIV-1 envelope-mediated cell-cell fusion. The inhibition is at the level of viral entry, specific for the HIV-1 envelope, and independent of virus tropism. In the previous studies, cell-free viruses of laboratory-adapted HIV-1 strains from subtype B were used to infect human CD4 T cell lines. To further test the effectiveness of this membrane-bound scFv (m-scFv) on HIV-1 infection, in this study, we carried out experiments to determine whether the m-scFv can neutralize infection of primary isolates from various HIV-1 subtypes and whether the m-scFv can neutralize HIV-1 captured and transferred by DC-SIGN on the surface of monocytic cell lines or DCs. We demonstrated that the m-scFv markedly inhibits primary isolates derived from various subtypes and significantly blocks HIV-1 captured and transferred by DC-SIGN on monocytic cell lines and on human DCs. Therefore, a nonneutralizing antibody acts as a broad neutralizing antibody when expressed on the cell surface, which significantly inhibits infection of both cell-free and DC-SIGN-captured and transferred virus. Our studies further point out the potential use of m-scFv as a inhibitor against HIV-1 transmission as well as a tool to dissect the mechanism of HIV-1 entry via DC-SIGN capture and transfer to CD4 T cells.


Distribution of vasopressin 1a and oxytocin receptor protein and mRNA in the basal forebrain and midbrain of the spiny mouse (Acomys cahirinus).
The nonapeptide system modulates numerous social behaviors through oxytocin and vasopressin activation of the oxytocin receptor (OXTR) and vasopressin receptor (AVPR1A) in the brain. OXTRs and AVPR1As are widely distributed throughout the brain and binding densities exhibit substantial variation within and across species. Although OXTR and AVPR1A binding distributions have been mapped for several rodents, this system has yet to be characterized in the spiny mouse (Acomys cahirinus). Here we conducted receptor autoradiography and in situ hybridization to map distributions of OXTR and AVPR1A binding and Oxtr and Avpr1a mRNA expression throughout the basal forebrain and midbrain of male and female spiny mice. We found that nonapeptide receptor mRNA is diffuse throughout the forebrain and midbrain and does not always align with OXTR and AVPR1A binding. Analyses of sex differences in brain regions involved in social behavior and reward revealed that males exhibit higher OXTR binding densities in the lateral septum, bed nucleus of the stria terminalis, and anterior hypothalamus. However, no association with gonadal sex was observed for AVPR1A binding. Hierarchical clustering analysis further revealed that co-expression patterns of OXTR and AVPR1A binding across brain regions involved in social behavior and reward differ between males and females. These findings provide mapping distributions and sex differences in nonapeptide receptors in spiny mice. Spiny mice are an excellent organism for studying grouping behaviors such as cooperation and prosociality, and the nonapeptide receptor mapping here can inform the study of nonapeptide-mediated behavior in a highly social, large group-living rodent.


Physiotherapy in Indian communities: a brief review.
Background: Importance of community rehabilitation in India has been emphasized in previous research. There is ample research that has been published for different communities in the country. However, the precise role of physiotherapy in community rehabilitation is unclear.The objective of the current brief report is to look into the role of physiotherapy in community rehabilitation. Methods: Relevant literature search was done using databases namely Medline, Scopus, PubMed, PEDro and CINAHL using search terms- India, community rehabilitation, home rehabilitation, home exercises and physiotherapy. Studies that followed the PICO format, published in English,after 2005 and that had specifically mentioned the role of physiotherapy in community projects were included. Results: While there are handful of studies that have mentioned the contribution of physiotherapy in the community, most of the interventions are targeted toward management of chronic health conditions. More work needs to be done to outline the importance and precise role of physiotherapy in the rehabilitation of communities in India, especially in preventive care.A model has been created to emphasize the holistic approach of physiotherapy in the Indian setting. Conclusion: Physiotherapy has a pivotal position in community rehabilitation in India.However, published research for the same is lacking. While physiotherapy interventions have been designed to target chronic health conditions in the community, emphasis on preventive care is lacking.


Glioma-related epilepsy in patients with diffuse high-grade glioma after the 2016 WHO update: seizure characteristics, risk factors, and clinical outcomes.
The aim of this study was to investigate the epidemiological characteristics, associated risk factors, and prognostic value of glioma-related epilepsy in patients with diffuse high-grade gliomas (DHGGs) that were diagnosed after the 2016 updated WHO classification was released. Data from 449 patients with DHGGs were retrospectively collected. Definitive diagnosis was reaffirmed according to the 2016 WHO classification. Seizure outcome was assessed using the Engel classification at 12 months after surgery. Univariate and multivariate analyses were performed to identify risk factors associated with preoperative and postoperative glioma-related epilepsy. Lastly, the prognostic value of glioma-related epilepsy was evaluated by Kaplan-Meier and Cox analysis. The incidence of glioma-related epilepsy decreased gradually as the malignancy of the tumor increased. Age < 45 years (OR 2.601, p < 0.001), normal neurological function (OR 3.024, p < 0.001), and lower WHO grade (OR 2.028, p = 0.010) were independently associated with preoperative glioma-related epilepsy, while preoperative glioma-related epilepsy (OR 7.554, p < 0.001), temporal lobe involvement (OR 1.954, p = 0.033), non-gross-total resection (OR 2.286, p = 0.012), and lower WHO grade (OR 2.130, p = 0.021) were identified as independent predictors of poor seizure outcome. Furthermore, postoperative glioma-related epilepsy, rather than preoperative glioma-related epilepsy, was demonstrated as an independent prognostic factor for overall survival (OR 0.610, p = 0.010). The updated WHO classification seems conducive to reveal the distribution of glioma-related epilepsy in DHGG patients. For DHGG patients with high-risk predictors of poor seizure control, timely antiepileptic interventions could be beneficial. Moreover, glioma-related epilepsy (especially postoperative glioma-related epilepsy) is associated with favorable overall survival.


New steroidal glycosides from Tribulus terrestris L.
Two new steroidal glycosides were isolated from Tribulus terrestris L. Their structures were elucidated as 26-O-β-D-glucopyranosyl-5α-furostan-12-one-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (1) and 26-O-β-D-glucopyranosyl-5α-furostan-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (2) by spectroscopic methods including 1D and 2D NMR experiments.


Hyaluronan as a Promising Biomarker for Myocardial Damage.
Hyaluronan is a glycosaminoglycan, one of the chief components of the extracellular matrix. The aim of the present study is to investigate plasma hyaluronan levels among patients with acute myocardial infarction (AMI). This prospective study enrolled 56 consecutive patients with AMI who underwent percutaneous coronary intervention within 2 hours after admission. Plasma levels of hyaluronan were measured at the time of admission (baseline), and on the 7th and 30th day after AMI. Echocardiographic examinations were performed at baseline and on the 30th day after AMI. The hyaluronan levels were 33.2 ± 3.1 ng/ml (mean ± SD) at baseline, increased on the 7th day (46.2 ± 5.9 ng/ml), and continued to remain high on the 30th day after AMI (50.1 ± 5.1 ng/ml). There were significant correlations of the hyaluronan levels between baseline and on the 7th day (r = 0.535, p < 0.001) and between baseline and on the 30th day (r = 0.263, p = 0.05). Significant correlations were also found between hyaluronan levels on the 30th day, and the peak levels of CK-MB (r = 0.429, p = 0.001) or highly sensitive troponin levels (r = 0.360, p = 0.006). The hyaluronan levels were significantly higher on the 30th day after AMI in patients with anterior infarction, but not in patients with non-anterior infarction (p = 0.01 vs. p = 0.653). In conclusion, this is the first report that demonstrates the increase of plasma hyaluronan levels among patients with AMI.


Anterior sacral meningocele contiguous with a pelvic hamartoma. Case report.
A patient with an anterior sacral meningocele combined with a hamartoma was diagnosed with x-ray films, myelography, and computerized tomography. She was successfully operated on by a transabdominal approach.


Cerebral antivasoconstrictive effects of flunarizine.
Flunarizine is a selective Ca++-antagonist with weaker H1-histaminergic antagonistic properties. Flunarizine reduces vasospasm caused by an exaggerated Ca++-influx in depolarized arteries and by vasoactive substances released from aggregating platelets. This Ca++-antagonist also antagonizes the mutual amplification of the vasoconstrictor action of the platelet products. Flunarizine is particularly effective in the cerebral blood vessels, also when they are hyperreactive because of hypoxia. The compound does not interfere with normal arteriolar autoregulation or heart function. Thus flunarizine may be particularly effective in preventing vasospasm without lowering blood pressure or inducing a steal phenomenon.


Indications and therapeutic management of carotid stenosis in high-risk patients: SAPPHIRE and beyond.
Carotid artery revascularization is an effective means of stroke prevention in selected patients with carotid stenosis. Traditionally, carotid endarterectomy (CEA) was performed to achieve this goal. With the development of endovascular techniques and technologies, carotid artery stenting (CAS) has become a viable alternative to CEA, particularly in patients considered high risk for CEA. The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) study single-handedly catapulted CAS to the forefront of therapeutic options for high-risk patients. This study directly compared CAS to CEA in high-risk patients, finding CAS to be equally effective. Since SAPPHIRE, several studies have confirmed the safety and efficacy of CAS in high-risk patients, demonstrating acceptable 1-year morbidity (1-11.3%) and durable target-vessel patency (97.6-98.7%).


Clinical management of latex allergy.
The use of latex gloves in the health care setting dates back to the 1800s, when these products were introduced as a means of preventing the passage of microorganisms to operating room patients. Today, fear of human immunodeficiency virus transmission and other blood-borne diseases has led to implementation of standardized guidelines for glove use for health care professionals. Because of the unique combination of strength, flexibility, and elasticity of natural rubber, latex is typically the material of choice for a variety of medical products, including examination gloves. Unfortunately, routine use of latex in the health care setting may be detrimental to patients and caregivers with a history of natural rubber latex hypersensitivity reactions.


Changes in the stability of specific mRNA species in response to growth stage in Bacillus subtilis.
In this study we compared the cellular concentrations and stability of the mRNA transcribed from the aprE (subtilisin) gene (a gene preferentially expressed in stationary growth phase) with those of a vegetative mRNA, succinate dehydrogenase (SDH) mRNA. The subtilisin transcript was shown to be at least 3 times more stable in early stationary phase than it is 2 hr further into stationary phase. When cells were shifted from maximum expression of the subtilisin transcript in stationary phase to physiological conditions, which allowed for the resumption of vegetative growth, the cellular concentration of the subtilisin mRNA decreased rapidly. We conclude that mRNA degradation is one of the means by which the cellular concentrations of the SDH and subtilisin transcripts are adjusted in response to growth stage.


Some temporal properties of behavioral contrast.
Pigeons were rewarded on a variable time interval for pecking a translucent key illuminated with either a 45 degrees or a vertical line. The key illumination changed every 2 min during daily 1-hr sessions. When the rates of pecking were stable, reinforcement was omitted in the presence of the 45 degrees line. Responding in the presence of the vertical line increased. This increase did not disappear when responses to the 45 degrees line were once more reinforced, but when reinforcements for responses in the presence of the 45 degrees line were again omitted, responding to the vertical line increased again. After the second alternation of these two procedures, the increased responding to the vertical line appeared when responses were not reinforced in the presence of the 45 degrees line, and disappeared when reinforcement was available during both stimuli. In a second experiment, the key illumination changed between sessions only, so that 1-hr sessions of reinforcement and non-reinforcement occurred on alternate days. Responding to the vertical line still increased when responding to the 45 degrees line was not reinforced, but the increase tended to disappear during the session.


[Expression of nuclear autoantigenic sperm protein in platinum resistance ovarian cancer cell clones].
To study the expression of NASP in platinum resistance ovarian cancer cell clones (C0C1/DDP). The proteins of C0C1 and C0C1/DDP were separated by highly sensitive two-dimensional differential gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF-MS) to identify the proteins differentially expressed in cisplatin sensitive and cisplatin resistance cell lines. The investigators found a group of the distinct expressed proteins between C0C1 and C0C1/DDP. Among them, NASP was one of the down-regulated proteins by 21% (Student's t-test; P = 0.01). The identification of NASP in C0C1/DDP has laid a foundation for future in-depth researches into the mechanisms of ovarian cancer platinum resistance.


Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2.
Skin is the outermost part of the body and is, thus, inevitably exposed to UV rays and environmental pollutants. Oxidative stress by these hazardous factors accelerates skin aging and induces skin inflammation and carcinogenesis. Aryl hydrocarbon receptors (AHRs) are chemical sensors that are abundantly expressed in epidermal keratinocytes and mediate the production of reactive oxygen species. To neutralize or minimize oxidative stress, the keratinocytes also express nuclear factor-erythroid 2-related factor-2 (NRF2), which is a master switch for antioxidant signaling. Notably, there is fine-tuned crosstalk between AHR and NRF2, which mutually increase or decrease their activation states. Many NRF2-mediated antioxidant phytochemicals are capable of up- and downmodulating AHR signaling. The precise mechanisms by which these phytochemicals differentially affect the AHR and NRF2 system remain largely unknown and warrant future investigation.


Subclinical hypothyroidism is associated with insulin resistance in rheumatoid arthritis.
We investigated the prevalence of subclinical hypothyroidism and its association with insulin resistance and other cardiovascular (CV) risk factors in rheumatoid arthritis (RA). We recorded thyroid function tests, insulin resistance markers comprising the Homeostasis Model Assessment for insulin resistance (HOMA-IR), the Quantitative Insulin Sensitivity Check Index (QUICKI) and triglycerides/high-density lipoprotein (HDL) cholesterol ratios, and other CV risk factors in 126 patients with RA. Fifteen (12%) were taking thyroxine for hypothyroidism and 14 (11%) had subclinical hypothyroidism (thyrotropin > 4 mU/L and normal free thyroxine levels). Compared to the 97 euthyroid patients, the QUICKI was lower and the HOMA-IR higher in treated (p = 0.031 for both) and subclinical (p = 0.004 for both) hypothyroid cases while the triglycerides/HDL cholesterol ratios were higher in subclinical (p = 0.039) but not in treated hypothyroid (p = 0.365) cases. Treated hypothyroid patients were more often hypertensive (n = 11 [75%]) than euthyroid patients (n = 36 [37%]) (p = 0.008). No other differences in characteristics were found among the three groups. After controlling for potentially confounding variables, subclinical hypothyroidism remained independently predictive of the HOMA-IR and QUICKI (p <or= 0.06) while treated hypothyroidism did not (p = 0.2). Subclinical hypothyroidism was commonly encountered and associated with insulin resistance and its related dyslipidemia in RA. Evaluation of thyroid function should be considered in future studies aimed at delineating CV risk in RA.


Hydroxy-Directed Enantioselective Hydroxyalkylation in the Carbocyclic Ring of Indoles.
A Cinchona-derived squaramide catalyzes the reaction between hydroxyindoles and isatins leading to enantioenriched indoles substituted in the carbocyclic ring. The reaction proceeds efficiently with differently substituted isatins, yielding the desired products with excellent regioselectivity, good yields, and high enantiocontrol. Moreover, every position of the carbocyclic ring of the indole can be functionalized by using the appropriate starting hydroxyindole. The OH group was removed smoothly upon hydrogenolysis of the corresponding triflate.


Using chemical exchange to assign non-covalent protein complexes in slow exchange with the free state: enhanced resolution and efficient signal editing.
The formation of a ligand-protein complex oftentimes results in significant chemical shift changes. These changes may occur not only in the binding pocket but also in distal regions of the protein target. Therefore the reassignment of the backbone resonances in the complex is frequently a time consuming challenge. Here we present a suite of resolution-enhanced N(z)-exchange NMR experiments useful for rapidly assigning backbone (1)H and (15)N amide resonances of the ligand-bound form of a protein in slow exchange with its free state. Incorporation of semi-constant time frequency labeling periods into 3D N(z)-exchange experiments in combination with the collection of resolution-enhanced 2D N(z)-exchange difference spectra leads to a powerful set of tools for analyzing protein-ligand complexes. This allows for both the assignment of the bound state and the rapid assessment of the protein binding interface. The proposed methodology is demonstrated on the complex formed by the dimerization-docking domain of the c-AMP-dependent protein kinase and the tethering domain of the dual-binding A-kinase anchoring protein (AKAP).


Saturation of the anomalous Hall effect in critically disordered ultrathin CNi3 films.
We demonstrate that a distinct high-disorder anomalous Hall effect phase emerges at the correlated insulator threshold of ultrathin, amorphous, ferromagnetic CNi3 films. In the weak-localization regime, where the sheet conductance G>>e{2}/h, the anomalous Hall resistance of the films increases with increasing disorder and the Hall conductance scales as G{xy} proportional to G{phi} with phi=1.6. However, at sufficiently high disorder the system begins to enter the 2D correlated insulator regime, at which point the Hall resistance R{xy} abruptly saturates and the scaling exponent becomes phi=2. Tunneling measurements show that the saturation behavior is commensurate with the emergence of the 2D Coulomb gap, suggesting that e-e interactions mediate the high-disorder phase.


Effect of intravenous infusion of blood on the electrocardiogram of anaesthetised dogs.
About 250 to 450 ml of blood was infused within 3 to 5 minutes to study the effect of rapid intravenous infusion of blood on electrocardiogram of 21 anaesthetised dogs. In 16 dogs with initial heart rate above 136/min, i.v. infusion resulted in bradycardia, decrease in P wave amplitude, increase in R wave amplitude and increase in PR, QT and ST intervals. In 3 dogs with initial heart rates above 136/min there was no change in the heart rate, while in 2 dogs with heart rate below 136/min there was tachycardia after the infusion.


Biosimilars: illustration of scientific issues in two examples.
Scientific issues and clinical implications associated with the use of biosimilars (biopharmaceuticals that are similar to an innovator product, notwithstanding minor differences) are illustrated in two examples, botulinum neurotoxins and erythropoietic agents. Comparison of Botox and Dysport, products that both contain botulinum toxin type A, revealed distinct differences in physicochemical characteristics, approved indications, dosing, and frequency of adverse events. Differentiating between botulinum toxin products on the basis of immunogenicity in the clinical setting would be of value in product selection, and pharmacists could play a valuable role in collecting antigenicity rate data and reporting them to the Food and Drug Administration (FDA) and the manufacturer. Various ethical and practical considerations are associated with the use of erythropoietic agents. The desire to optimize patient care and outcomes must be weighed against the likelihood of obtaining reimbursement for erythropoietic therapy, and reimbursement policies vary from one state to another. Comparing erythropoietic agents requires the use of a consistent and valid definition of treatment response. The definition of response that FDA will accept in the future when evaluating applications for approval of new biosimilar erythropoietic agents and establishing equivalence remains to be determined. A variety of scientific and practical clinical issues are associated with the use of biosimilars, including product differences in physicochemical characteristics, reimbursement policies, and the need for valid and clinically relevant criteria for comparing the efficacy and safety of biosimilars and innovator products.


Prediction of restenosis after coronary balloon angioplasty. Results of PICTURE (Post-IntraCoronary Treatment Ultrasound Result Evaluation), a prospective multicenter intracoronary ultrasound imaging study.
Intracoronary ultrasound (ICUS) imaging is potentially suitable to identify lesions at high risk of restenosis after percutaneous transluminal coronary angioplasty (PTCA), but it has not been studied systematically. We recruited 200 patients in whom ICUS studies were performed after successful PTCA and related their ICUS parameters to 6-month follow-up quantitative coronary angiography. This was performed in 164 patients (82%), yielding 170 lesions for analysis. The overall incidence of a > or = 50% diameter stenosis at follow-up (categorical restenosis) was 29.4%. Quantitative ICUS parameters were weakly but significantly related to follow-up minimal luminal diameter on quantitative coronary angiography (lumen area: R2 = .36, P = .0001; vessel area: R2 = .29, P = .0002; plaque area: R2 = -.18, P = .021; percent obstruction: R2 = -.15, P = .05), but categorical restenosis was not significantly related to these parameters (P = .63, .77, .38, and .08, respectively). There were no significant predictors of restenosis in ICUS parameters of plaque morphology: eccentric versus concentric (P = 1.0), plaque type (hard, soft, or calcific, P = .98), or the number of calcified quadrants (P = .41). There were no significant predictors of restenosis in two predefined types of vessel-wall disruptions: (1) rupture: presence (P = .79), depth (partial versus complete, P = .85), or extent in quadrants (P = .6), and (2) dissection: presence (P = .31), depth (P = .82), or extent (P = .38). Qualitative ICUS parameters after PTCA did not predict restenosis. A larger lumen and vessel area and a smaller plaque area by ICUS were associated with a larger angiographic minimal lumen diameter at follow-up, but these parameters were not significantly related to categorical restenosis.


[Esophageal variceal pressure by endoscopic pneumatic pressure sensor in patients with liver cirrhosis].
The esophageal variceal pressure was determined by endoscopic pneumatic pressure sensor method in patients with liver cirrhosis, complicating esophageal varices. The variceal pressure by this method was significantly correlated with percutaneous transhepatic portal venous pressure. The variceal pressure was related with endoscopic findings of varices, especially of red-color sign, form and location. The variceal pressure below 200 mmH2O showed negligible risk of variceal bleeding, and the pressure over 350 mmH2O was associated with high risk of variceal bleeding. These results indicate that esophageal variceal pressure by this method may provide useful informations in natural history of esophageal varices.


Non covalent interactions stabilizing the chiral dimer of CH2ClF: a rotational study.
We report the rotational spectra of three isotopologues of the dimer of chlorofluoromethane, namely CH235ClF-CH235ClF, CH235ClF-CH237ClF and CH237ClF-CH235ClF. The assigned (most stable) conformer is chiral (C1 symmetry) and displays a network of two C-HCl-C and one C-HF-C weak hydrogen bonds, combined with a ClF halogen bond. The hyperfine structures due to the quadrupolar effects of the two non-equivalent 35Cl (or 37Cl) atoms have been fully resolved, leading to an accurate determination of two sets of diagonal and of some mixed quadrupole coupling constants. Information on the rs positions of the two Cl atoms and on the structural parameters of the hydrogen bonds has been obtained. The dissociation energy of the complex has been estimated as 5.9 kJ mol-1.


Structural and molecular characterization of dynein in a gall-midge insect having motile sperm with only the outer arm.
The dipteran Monarthropalpus flavus possesses a peculiar sperm axoneme, characterized by multiple rows of microtubular doublets linked by the outer dynein arms only, lacking any equivalent of the central pair/radial spoke complex. The structure of these dynein molecules was studied by electron microscopy (EM). Using the quick-freeze, deep-etch method of EM, they were found to be similar to outer dynein arms described previously. Two globular "heads," each subdivided by a cleft, are clearly discernible. "Stalks" extend from proximal head to contact the B-tubule of the adjacent doublet. Unlike the situation in vertebrate sperm, the stalks sometimes branch into two thinner strands that contact the B-tubule at different sites. Treatment of demembranated sperm cells with ATP and vanadate induces conformational changes in the dynein outer arms. These are interpreted as the result of rotation of the dynein head with respect to what is observed in axonemes in rigor condition (after ATP depletion). SDS-PAGE indicates that the high-molecular-weight complement of this molecule comprises a single heavy chain. Specific dynein heavy chain-related DNA sequences corresponding to the catalytic-phosphate binding region were amplified by RT-PCR. Only one axonemal dynein sequence was identified among all amplified fragments. Southern blot analysis performed on genomic DNA using this sequence as a probe identified two hybridizing genes, only one of which is able to encode a functional product. Thus, genetic analysis indicates that this axonemal outer arm dynein is a homodymer of a single heavy chain subunit. In vivo, spermatozoa of this species are stored in a rolled configuration in female spermatheca, where they move rapidly with a wave-like motion. This movement could not be reproduced in vitro, except when spermatozoa were constrained in a bent configuration by some mechanical impediment. We propose that, in the absence of both the central pair/radial spoke complex and the inner arms, a curvature-dependent activation acts to trigger motility in these spermatozoa.


Primary osseous tumors of the pediatric spinal column: review of pathology and surgical decision making.
Spinal column tumors are rare in children and young adults, accounting for only 1% of all spine and spinal cord tumors combined. They often present diagnostic and therapeutic challenges. In this article, the authors review the current management of primary osseous tumors of the pediatric spinal column and highlight diagnosis, management, and surgical decision making.


Parameter estimation in biochemical pathways: a comparison of global optimization methods.
Here we address the problem of parameter estimation (inverse problem) of nonlinear dynamic biochemical pathways. This problem is stated as a nonlinear programming (NLP) problem subject to nonlinear differential-algebraic constraints. These problems are known to be frequently ill-conditioned and multimodal. Thus, traditional (gradient-based) local optimization methods fail to arrive at satisfactory solutions. To surmount this limitation, the use of several state-of-the-art deterministic and stochastic global optimization methods is explored. A case study considering the estimation of 36 parameters of a nonlinear biochemical dynamic model is taken as a benchmark. Only a certain type of stochastic algorithm, evolution strategies (ES), is able to solve this problem successfully. Although these stochastic methods cannot guarantee global optimality with certainty, their robustness, plus the fact that in inverse problems they have a known lower bound for the cost function, make them the best available candidates.


Luminal feedback regulation, monitor peptide, CCK-releasing peptide, and CCK receptors.
We summarize the discovery of luminal feedback regulation of pancreatic secretion in rats and its history. In rats, removal of proteolytic activity from the intestine produced a significant increase in pancreatic protein (enzyme) output. This increase was confirmed to be mediated by circulating cholecystokinin (CCK). Subsequently, two CCK-releasing peptides, monitor peptide and luminal CCK-releasing factor (LCRF), were purified from the rat pancreatic juice and small intestine, respectively, to elicit CCK release in luminal feedback regulation. Furthermore, we emphasize the important physiologic roles of CCK and CCK receptors by the discovery of disrupted CCK-A-receptor gene in rats. These findings should help to determine the regulation of pancreatic secretion and CCK functions in humans.


[Evaluation of pancreatic ductal decompression procedure for patients with advanced chronic pancreatitis, mainly from the viewpoint of pancreatic ductal changes].
Several pancreatic ductal decompression procedures have been applied for chronic pancreatitis. Unresolved problems, however, remain, i.e., to select the appropriate procedure among several different decompression procedures, to investigate the changes of pancreatic endocrine and exocrine functions resulting from such procedures, etc. In this paper we evaluated these problems, mainly by comparing conditions of the pancreatic duct as seen with pre- and post-operative endoscopic retrograde pancreatography (ERP). We classified the pancreatic duct of patients with chronic pancreatitis into seven types. This classification was devised so that the selection of the suitable operative procedure could be made. The severity of the abnormal ductal change was also evaluated. Eighteen patients were studied with reference to the post-operative change in the pancreatic duct and the patency of the pancreaticoenteral anastomosis in each procedure. Postoperative ERP showed good patency in the patients with lateral pancreaticojejunostomy and modified bilateral pancreaticojejunostomy, both having long anastomotic stoma. Among the findings of postoperative pancreatic ductal changes, the dilatation of the main duct was reduced in most of the patients, while the stenosis of the main duct remained unchanged in nearly all the patients. The duct in the tail area showed the best results, which suggested the importance of preservation of the pancreatic tail.


In vivo pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies in immune-mediated necrotising myopathy.
In autoimmunity, autoantibodies (aAb) may be simple biomarkers of disease or true pathogenic effectors. A form of idiopathic inflammatory myopathy associated with anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) aAb has been individualised and is referred to as immune-mediated necrotising myopathy (IMNM). The level of aAb correlates with IMNM activity and disease may respond to immunosuppression, suggesting that they are pathogenic. We aimed to evaluate the pathogenicity of IgG from patients with anti-SRP or anti-HMGCR aAb in vivo by developing the first mouse model of IMNM. IgG from patients suffering from anti-SRP or anti-HMGCR associated IMNM were passively transferred to wild-type, Rag2-/- or complement C3-/- mice. Muscle deficiency was evaluated by muscle strength on electrostimulation and grip test. Histological analyses were performed after haematoxylin/eosin staining or by immunofluorescence or immunohistochemistry analysis. Antibody levels were quantified by addressable laser bead assay (ALBIA). Passive transfer of IgG from patients suffering from IMNM to C57BL/6 or Rag2-/- mice provoked muscle deficiency. Pathogenicity of aAb was reduced in C3-/- mice while increased by supplementation with human complement. Breakage of tolerance by active immunisation with SRP or HMGCR provoked disease. This study demonstrates that patient-derived anti-SRP+ and anti-HMGCR+ IgG are pathogenic towards muscle in vivo through a complement-mediated mechanism, definitively establishing the autoimmune character of IMNM. These data support the use of plasma exchanges and argue for evaluating complement-targeting therapies in IMNM.


Peroral Cholangioscopy-Guided Forceps Biopsy and Endoscopic Scraper for the Diagnosis of Indeterminate Extrahepatic Biliary Stricture.
Peroral cholangioscopy (POCS) has become a widely-used technique in diagnosing indeterminate biliary strictures, enabling optical viewing of the biliary system and targeted biopsies under direct vision. The diagnostic utility of the new endoscopic scraper, Trefle®, for extrahepatic cholangiocarcinoma (ECC) has also been reported. However, the diagnostic utility of POCS-guided and Trefle®-assisted tissue acquisition for ECC has never been compared empirically. We evaluated the efficacy and safety of Trefle®-assisted tissue acquisition for diagnosing ECC compared with POCS-guided tissue sampling. Patients who underwent Trefle®-assisted tissue acquisition or POCS-guided forceps biopsy to differentiate ECC from benign biliary disease between April 2014 and March 2018 were enrolled retrospectively. We evaluated the diagnostic performance of Trefle®-assisted tissue acquisition and POCS-guided forceps biopsy based on pathological evaluation. We also compared adverse events associated with Trefle®-assisted tissue acquisition with those of POCS-guided forceps biopsy. We enrolled 34 patients with biliary disease and performed Trefle®-assisted tissue acquisition and POCS-guided forceps biopsy in 14 and 20 patients, respectively. Sensitivity, specificity, and accuracy of Trefle®-assisted tissue acquisition were 87.5%, 83.3%, and 85.7%, respectively, and for POCS-guided forceps biopsy, these were 90.0% each. Statistical values of Trefle®-assisted tissue acquisition and POCS-guided tissue acquisition were not significantly different. There were no significant differences in the occurrence of adverse events between the Trefle®-assisted tissue acquisition and the POCS-guided forceps biopsy (35.7% vs. 25.0%, p = 0.770). Compared with patients who underwent POCS procedure, endoscopic sphincterotomy was performed for fewer patients who underwent Trefle®-assisted tissue acquisition (p < 0.001). The diagnostic ability of Trefle®-assisted tissue acquisition for ECC is similar to that of POCS-guided tissue acquisition. Trefle®-assisted tissue acquisition might also help to preserve the sphincter of Oddi and its digestive function.


Modulation of the Plasma Kallikrein-Kinin System Proteins Performed by Heparan Sulfate Proteoglycans.
Human plasma kallikrein-kinin system proteins are related to inflammation through bradykinin. In the proximity of its target cells, high molecular weight kininogen (H-kininogen) is the substrate of plasma kallikrein, which releases bradykinin from H-kininogen. Heparan sulfate proteoglycans (HSPGs) play a critical role in either recruiting kinin precursors from the plasma, or in the assembly of kallikrein-kinin system components on the cell surface. Furthermore, HSPGs mediate the endocytosis and activation of H-kininogen and plasma prekallikrein. In the presence of HSPGs (Chinese hamster ovary cell, CHO-K1, wild type cells) both heparin and heparan sulfate strongly inhibit the H-kininogen interaction with the cell membrane. H-kininogen is internalized in endosomal acidic vesicles in CHO-K1 but not in CHO-745 cells (mutant cells deficient in glycosaminoglycan biosynthesis). The endocytosis process is lipid raft-mediated and is dependent on caveolae. Both types of CHO cells do not internalize bradykinin-free H-kininogen. At pH 7.35, bradykinin is released from H-kininogen on the surface of CHO-745 cells only by serine proteases; however, in CHO-K1 cells either serine or cysteine proteases are found to be involved. The CHO-K1 cell lysate contains different kininogenases. Plasma prekallikrein endocytosis in CHO-K1 cells is independent of H-kininogen, and also prekallikrein is not internalized by CHO-745 cells. Plasma prekallikrein cleavage/activation is independent of glycosaminoglycans but plasma kallikrein formation is more specific on H-kininogen assembled on the cell surface through glycosaminoglycans. In this mini-review, the importance of HSPGs in the regulation of plasma kallikrein-kinin system proteins is shown.


Conservative management of pelvic sepsis with severe shock and multiple organ dysfunction syndrome after rubber-band ligation of internal haemorrhoids: surgery is not the only option.
Rubber-band ligation (RBL) is a safe and cost-effective approach to internal haemorrhoids. Potential side effects include pain, bleeding, urinary retention and occasionally pelvic sepsis and systemic inflammatory response syndrome (SIRS). At-risk patients are mainly those with immunocompromising conditions. Although aggressive surgical debridement or diverting colostomy appear to be obvious options when patients' life is threatened, their superiority to conservative measures has not been proven. We present the case of a 58-year-old female patient who presented 48 h after a RBL with pelvic pain, dysuria and leukocytosis. Her condition deteriorated rapidly that ventilator and inotropic support were required for a severe SIRS for almost 10 days. Laparoscopic exploration and imaging showed a rectosigmoiditis, ascites and superficial rectal necrosis with no transmural damage requiring an emergent surgery. Conservative management could possibly be a valid option in post-RBL pelvic sepsis even when severe associated multiple organ failure is present.


[Mechanisms of action and clinical effectiveness of ultratonotherapy in the complex treatment of foot onychomycosis].
A long course of onychomycosis, severe hyperkeratosis, slow growth of the nails of the feet, somatic burden, as well as an increase in the resistance of pathogens often lead to a decrease in the effectiveness of traditional antimycotics, dictating the need to create new methods of therapy. A promising direction of treatment is the use of alternating current of supratonal frequency of high voltage and low power - ultratonotherapy (UT) in combination with antifungal drugs. The article presents data on the mechanisms of action and clinical effectiveness of this method in the complex treatment of foot onychomycosis. To study the mechanisms of action and evaluate the clinical effectiveness of UT in the complex treatment of foot onychomycosis. The antifungal effect of UT was studied in the colonies of Trichophyton rubrum and Candida albicans. The distribution of ozone released during the procedure on the affected nail plate was evaluated in vitro using a qualitative chemical reaction and photodermatoscopy. The state of tissue blood flow in the periungual tissues under the influence of UT was studied in vivo by means of ultrasound dopplerographic scanning (USDGS). The clinical effectiveness of the method was evaluated according to the results of complex treatment of patients with foot onychomycosis in comparison with traditional methods of therapy. UT has both fungicidal and fungistatic effects. With a qualitative reaction to ozone, coloring of the surface and small structures of the nail plate was noted. According to the USDGS, after the use of UT, a significant increase in blood supply to the periungual tissues was recorded. The combined use of alternating current of a high voltage ultrasonic frequency with antifungal drugs in patients with foot onychomycosis contributes to the rapid growth of the nail and shorten the duration of mycological cure. UT has an antifungal effect and improves microcirculation in the area of the nail bed. In the complex treatment of patients with foot onychomycosis, the method accelerates clinical and mycological cure, stimulates nail growth, which reduces the rate of systemic and local antifungal therapy.


Phase II trial of vindesine in patients with squamous cell cancer of the head and neck.
Fifteen patients with advanced squamous cell cancer of the head and neck received weekly vindesine at doses of 3 mg/m2. No patient had received prior chemotherapy, though all had received either radiotherapy or radiotherapy and surgery. Fourteen patients were evaluable for response. Two patients had documented partial remissions. Dose-limiting neutropenia was the primary toxic effect observed. It was frequent and occasionally life-threatening. Vindesine has minor but real activity in this group of patients with advanced head and neck cancer who have not received prior chemotherapy.


Paraphenylenediamine (PPD) Poisoning Mistaken for an Anaphylactic Reaction.
Paraphenylenediamine (PPD) is commonly used in parts of Africa and Asia in combination with Lawsonia alba leaves (also widely known as henna) or as a substitute to dye the hair, palms, soles, or arms for wedding ceremonies or spiritual events. At the same time, it is quickly trending as an agent for suicidal attempts through ingestion. Toxicity is dose-dependent and can lead to serious complications both locally, such as angioedema and airway swelling, or systemically such as acute kidney injury, fatal arrhythmias, and acute hepatitis. We present a case of a 26-year-old pregnant female patient, with no known underlying medical history or known allergies. She ingested PPD-based dye in an attempt to end her life. She initially presented asymptomatically but started developing delayed toxicity symptoms including angioedema and acute liver failure. Her initial diagnosis was an anaphylaxis reaction, and her workup and management were conducted accordingly. We discuss the appropriate course of action in terms of investigations and management in cases of PPD poisoning, and what measures should have been taken in this patient to provide the best healthcare outcome.


Immune-associated molecular occurrence and prognosis predictor of hepatocellular carcinoma: an integrated analysis of GEO datasets.
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of cancer-related deaths worldwide. As immune response failure is the main factor in the occurrence and poor prognosis of HCC, our study aimed to develop an immune-associated molecular occurrence and prognosis predictor (IMOPP) of HCC. To that end, we discovered a 4-gene immune-associated gene signature: C-C motif chemokine ligand 14 (CCL14), kallikrein B1 (KLKB1), vasoactive intestinal peptide receptor 1 (VIPR1), and cluster of differentiation 4 (CD4). When tested on three cohorts as an immune-associated molecular occurrence predictor (IMOP), it had high sensitivity, specificity, and area under the receiver operating characteristics curve. When tested as an immune-associated molecular prognosis predictor (IMPP), it stratified the HCC prognosis for overall survival (Kaplan-Meier analysis, log rank P = 0.0016; Cox regression, HR = 1.832, 95% CI = 1.173-2.859, P = 0.008) and disease-free survival (Kaplan-Meier analysis, log rank P = 0.0227). IMPP also significantly correlated with the clinicopathological characteristics of HCC; integrating it with clinicopathological characteristics improved the accuracy of a nomogram for overall survival prediction (C-index: 0.7097 vs. 0.6631). In HCC tumor microenviroments, the proportion of CD8+ T cells significantly differed between IMOP-stratified groups. We conclude that IMOPP can potentially predict the occurrence of HCC in high-risk populations and improve prognostic accuracy by providing new biomarkers for risk stratification. In addition, we believe that the IMOP mechanism may be related to its effect on the proportion of CD8+ T cells in tumor-infiltrating lymphocytes.


Tumor-associated macrophages as a prognostic parameter in multiple myeloma.
The interaction between multiple myeloma (MM) cells and the bone marrow stroma constitutes the basis of myeloma pathogenesis and has led the way for the corresponding therapeutic strategies. The aim of this study is to evaluate tumor-associated macrophages (TAMs) which is an important element of bone marrow stroma and its prognostic relevance in newly diagnosed MM patients. We also wanted to determine the association between TAMs and microvessel density (MVD). Sixty-eight patients, who were diagnosed with MM at the Department of Hematology, Gazi University Hospital, between January 2000 and January 2011, were reviewed retrospectively. Tumor-associated macrophages were evaluated by staining with anti-CD68 and anti-CD163 monoclonal antibodies, and MVD was evaluated by factor VIII staining. Median age was 60 (range, 40-84) years with 36 males and 32 females. The number of both CD 68+ and CD 163+ cells had a negative impact on OS at 6 years (p = 0.013 vs. 0.036; p = 0.015 vs. 0.039) in univariate and multivariate analysis in which age, sex, ISS, the induction treatment, and response to induction treatment are included as variables. High-grade MVD was found to be associated with increased CD163+ cell count. In conclusion, TAMs seems to be a promising prognostic histopathological marker in newly diagnosed MM patients.


Sudden infant death syndrome: parents' perceptions and responses to the loss of their infant.
Sudden Infant Death Syndrome (SIDS) is the number one killer of infants under one year of age. Families are left in a state of crisis after a baby dies of SIDS. Thus, crisis counseling has been offered routinely to SIDS parents in King County, Washington. The purpose of this retrospective study was to assess whether mothers differed significantly from fathers in their perception of the situation, their feelings experienced and expressed, their approaches to problem solving, and the support they received. Differences in reactions between single and married parents were also studied. The 48% return rate produced a sample of 54 parents, 37 mothers and 17 fathers, who had lost their infant to SIDS. Statistically significant differences were found between mothers and fathers, as well as between single and married parents, in their view of the SIDS event, their problem solving approaches, and support systems. The results provide useful information for nurses in counseling SIDS parents and in working with families during and after subsequent pregnancies.


Selenite-stress selected mutant strains of probiotic bacteria for Se source production.
Selenium deficiency is a major health problem worldwide for about 1 billion people. Bacterial cells usually possess low tolerance to selenite stress and also low ability to reduce high concentrations of toxic selenite. Here, high tolerance to selenite and selenium bioaccumulation capability were developed in mutated clones of probiotic and starter bacteria including Enterococcus faecium, Bifidobacterium animalis ssp. lactis, Lactobacillus casei and Lactococcus lactis ssp. lactis by food-level strain development process and clone selection. All mutant clones possessed increased glutathione concentration and glutathione reductase activity. The selenite treatment increased further these values in L. casei mutant strain pointing at a different selenite reduction pathway and/or stress response in this organism. Considerable conversion of selenite to cell bound selenium forms with a concomitant high biomass production was detected in E. faecium and B. animalis ssp. lactis cultures. Possible application of these strains as food and feed supplements is under investigation.