Iron Oxide Nanoparticle-Powered Micro-Optical Coherence Tomography for in Situ Imaging the Penetration and Swelling of Polymeric Microneedles in the Skin.
In recent years, polymeric microneedles (MNs) have attracted keen interests among researchers because of their applicability in transdermal drug delivery and interstitial skin fluid (ISF) extraction. When designing and characterizing such devices, it is critical to monitor their real-time in vitro and in vivo performances to optimize the desired effects, yet most of the existing methods are incapable of such functions. To address this unmet need, we develop a real-time noninvasive imaging methodology by integrating iron oxide (Fe3O4) nanoparticles into polymeric MNs to enhance image contrast for micro-optical coherence tomography (μOCT) imaging. Using the Fe3O4-integrated polystyrene-block-poly(acrylic acid) (PS-b-PAA) MNs as an example, we evaluate the influences of Fe3O4 concentrations on contrast enhancement in μOCT imaging and visualize the real-time swelling process of polymeric MNs in biological samples for the first time. Our results show that a concentration of ∼4-5 wt % Fe3O4 nanoparticles not only helps achieve the best contrast-to-noise ratio in μOCT imaging, which is 10 times higher than that without Fe3O4 nanoparticles in air and hydrogel, but also enables the real-time changes in the profile of MNs to be observed clearly in their swelling process in skin tissues. On the basis of such findings, we utilize the optimized concentration of Fe3O4 nanoparticles to further quantitatively study the swelling kinetics of PS-b-PAA MNs in agarose hydrogel and fresh skin tissues, which lasts ∼20 and ∼30-35 s, respectively. The suitability of such a methodology for enhancing μOCT imaging would greatly facilitate the development and clinical translation of MN-based medical technologies.


Comparisons of carcinogenicities of nickel compounds in rats.
This study demonstrates marked differences in the incidences of sarcomas in Fischer rats within 2 years after a single im injection of 4 insoluble nickel-containing powders: amorphous nickel monosulfide (NiS), nickel subsulfide (alphaNi3S2), partially converted nickel-iron sulfide matte, and metallic nickel. The powders (less than 2 um median particle diameters) were administered in penicillin suspension, and each powder was tested at 2 dosages. Whereas alphaNi3S2 was highly carcinogenic, amorphous NiS did not induce any tumors. The carcinogenic potency of partially converted nickel-iron sulfide matte was less than alphaNi3S2 but greater than Ni powder. No sarcomas occurred at the injection site in two groups of control rats that received im injections of penicillin or Fe powder. The observed differences in carcinogenic potencies of alphaNi3S2 and amorphous NiS may provide an experimental approach to elucidate the molecular mechanisms of nickel carcinogenesis.


Artificial intelligence in the diagnosis and management of colorectal cancer liver metastases.
Colorectal cancer (CRC) is the third most common malignancy worldwide, with approximately 50% of patients developing colorectal cancer liver metastasis (CRLM) during the follow-up period. Management of CRLM is best achieved via a multidisciplinary approach and the diagnostic and therapeutic decision-making process is complex. In order to optimize patients' survival and quality of life, there are several unsolved challenges which must be overcome. These primarily include a timely diagnosis and the identification of reliable prognostic factors. Furthermore, to allow optimal treatment options, a precision-medicine, personalized approach is required. The widespread digitalization of healthcare generates a vast amount of data and together with accessible high-performance computing, artificial intelligence (AI) technologies can be applied. By increasing diagnostic accuracy, reducing timings and costs, the application of AI could help mitigate the current shortcomings in CRLM management. In this review we explore the available evidence of the possible role of AI in all phases of the CRLM natural history. Radiomics analysis and convolutional neural networks (CNN) which combine computed tomography (CT) images with clinical data have been developed to predict CRLM development in CRC patients. AI models have also proven themselves to perform similarly or better than expert radiologists in detecting CRLM on CT and magnetic resonance scans or identifying them from the noninvasive analysis of patients' exhaled air. The application of AI and machine learning (ML) in diagnosing CRLM has also been extended to histopathological examination in order to rapidly and accurately identify CRLM tissue and its different histopathological growth patterns. ML and CNN have shown good accuracy in predicting response to chemotherapy, early local tumor progression after ablation treatment, and patient survival after surgical treatment or chemotherapy. Despite the initial enthusiasm and the accumulating evidence, AI technologies' role in healthcare and CRLM management is not yet fully established. Its limitations mainly concern safety and the lack of regulation and ethical considerations. AI is unlikely to fully replace any human role but could be actively integrated to facilitate physicians in their everyday practice. Moving towards a personalized and evidence-based patient approach and management, further larger, prospective and rigorous studies evaluating AI technologies in patients at risk or affected by CRLM are needed.


The analysis of neurovascular remodeling in entorhino-hippocampal organotypic slice cultures.
Ischemic brain injury is among the most common and devastating conditions compromising proper brain function and often leads to persisting functional deficits in the affected patients. Despite intensive research efforts, there is still no effective treatment option available that reduces neuronal injury and protects neurons in the ischemic areas from delayed secondary death. Research in this area typically involves the use of elaborate and problematic animal models. Entorhino-hippocampal organotypic slice cultures challenged with oxygen and glucose deprivation (OGD) are established in vitro models which mimic cerebral ischemia. The novel aspect of this study is that changes of the brain blood vessels are studied in addition to neuronal changes and the reaction of both the neuronal compartment and the vascular compartment can be compared and correlated. The methods presented in this protocol substantially broaden the potential applications of the organotypic slice culture approach. The induction of OGD or hypoxia alone can be applied by rather simple means in organotypic slice cultures and leads to reliable and reproducible damage in the neural tissue. This is in stark contrast to the complicated and problematic animal experiments inducing stroke and ischemia in vivo. By broadening the analysis to include the study of the reaction of the vasculature could provide new ways on how to preserve and restore brain functions. The slice culture approach presented here might develop into an attractive and important tool for the study of ischemic brain injury and might be useful for testing potential therapeutic measures aimed at neuroprotection.


Inhibition of human digestive enzymes by hydrogenated malto-oligosaccharides.
Maltose, malto-oligosaccharides and their reduced sugar analogues have been tested as substrates and inhibitors of human salivary alpha-amylase and small intestine alpha-glucosidases. - Maltotriose and maltotetraose as well as their reduced analogues inhibited competitively alpha-amylase. Maltitol, maltotriitol and maltotetraitol were not hydrolyzed. - The small intestine maltases hydrolyzed maltitol at a very low rate, but maltotriitol was split almost at the same rate as maltotriose. These three sugars were weak mutual inhibitors. - The small intestine glucoamylase was slightly inhibited by maltotriitol but not by maltitol whereas fungal glucoamylase activity was strongly competitively inhibited by maltitol. This study shows that where the reducing end glucose unit of the malto-oligosaccharides below five glucose units are converted into sorbitol, their inhibitory effect is retained but their capacity of hydrolysis is reduced or disappears.


Wireless optical power transfer system by spatial wavelength division and distributed laser cavity resonance.
A novel wireless optical power transfer (WOPT) system using diverging angular dispersion and spatially distributed laser cavity resonance is proposed. In the transmitter, a diffraction grating spatially disperses the broadband light from a semiconductor optical amplifier. Receiving units spread across a wide field of view are embedded with retroreflecting beam splitters that reflect the incident beam back to the transmitter, thereby completing multiple resonant cavities. Retroreflectors enable a user-friendly alignment and tap power from the resonating cavity, supplying optical power. We demonstrate an automatic safety mechanism that instantly ceases the cavity resonance should any vulnerable organ break the transmitter-receiver line of sight. The results indicate that a single-channel WOPT system can provide a resonating average power of 17.2 mW (receiving power of 1.7 mW to the photodetector) over a distance of 1 m with a channel linewidth of 0.035 nm. For a proof-of-principle experiment, seven receiver units were successfully demonstrated to supply optical power. With careful retroreflector design and field-of-view optimization, the potential of our scheme can be further exploited toward commercial deployment.


Transradial and transfemoral coronary angiography and interventions: 1-year outcomes after initiating the transradial approach in a cardiology training program.
Limited data are available regarding the safety and feasibility of initiating transradial (TR) diagnostic coronary angiography (CA) and percutaneous coronary intervention (PCI) in cardiology fellowship programs. From July 2010 to June 2011, University of California, Davis Medical Center, adopted the TR approach with supervised cardiology fellows as the primary operators. Procedural variables and clinical outcomes of TR and transfemoral (TF) procedures were compared. To minimize confounding variables, ST-elevation myocardial infarction, bypass graft interventions, chronic total occlusions, and procedures with concomitant right heart catheterizations were excluded. To reflect the learning curve of the TR approach, this experience was assessed in 2 sequential 6-month periods. A total of 402 diagnostic CAs and 255 PCIs were included. Transradial access was used in 141 (35%) of the CAs and in 72 (28%) of PCIs. Within the TR-CA and TF-CA (n = 261) groups, there was no difference between fluoroscopy (10.4 ± 6.0 vs 11.0 ± 8.9, P = .63) or procedure (31.8 ± 11.5 vs 33.2 ± 13.8, P = .55) time throughout the academic year with a significant trend toward lower contrast use (128 ± 52 vs 110 vs 50, P = .04) by the second half. In addition, during the second half of the academic year, the TR-CA showed significantly higher fluoroscopy (11.0 ± 8.9 vs 6.7 ± 6.8, P = .001) and procedure (33.2 ± 13.8 vs 27.2 ± 11.6, P = .0015) times when compared with TF-CA. Transfemoral PCI (n = 183) and TR-PCI showed no significant difference between all fluoroscopy and procedure time and contrast use when comparing the 2 halves of the academic year. When comparing TF with TR within each academic half year, there was no difference within the PCI group. Vascular complications were less with the TR approach. Overall procedural success rates were high, and there were low rates of crossover and periprocedural complications in both the TR and the TF groups. A TR approach is safe for CA and PCI when performed by supervised operators in training. Although the learning curve for trainees appears slower for TR-CA compared with TF-CA, cardiology fellowship training programs should be encouraged to adopt TR procedures as part of their curriculum.


Case Report: Diabetic Foot Ulcer Infection Treated with Topical Compounded Medications.
An adult diabetic male with three toes amputated on his right foot presented with an ulcer infection on his left foot, unresponsive to conventional antifungal oral medication for over two months. The ulcerated foot wound had a large impairment on the patient's quality of life, as determined by the Wound-QoL questionnaire. The compounding pharmacist recommended and the physician prescribed two topical compounded medicines, which were applied twice a day, free of charge at the compounding pharmacy. The foot ulcer infection was completely resolved following 13 days of treatment, with no longer any impairment on the patient's quality of life. This scientific case study highlights the value of pharmaceutical compounding in current therapeutics, the importance of the triad relationship, and the key role of the compounding pharmacist in diabetes care.


Evaluation and Comparison of Impact Strength and Transverse Strength of Heat Polymerized Polymethylmethacrylate (PMMA) Denture Base Resin Repaired Using Heat Polymerizied PMMA Denture Base Resin, Auto-Polymerized PMMA Resin and A New Light Polymerizied Denture Resin: An In Vitro Study.
Repaired denture prosthesisdemands adequate transverse and impact strength. A new repairdenture base resin- "Lukafix" require to fulfil these criteria. This study evaluates and compares the transverse and impact strength of heat polymerizing, auto polymerizing and LUKAfix denture resin. 20 specimens were control(without repair), and other were test specimens which were fractured and repaired with heat polymerized PMMA resin, chemically polymerized PMMA resin and LUKAfix light polymerizing denture resin. Each group wasdivided in two subgroups. Subgroup A was subjected to transverse strength test and subgroup B to impact strength test. One way ANOVA was used to identify the mean difference among the four groups. Post-Hoc-Bonferroni was done to observe the difference between the groups. Maximum transverse strength was observed in specimens repaired with heat polymerized (48.33 ± 9.19) and least in LUKAfix denture resin (6.56 ± 1.15). Also, impact strength was maximum for heat polymerized (3.64 ± 0.41) followed by LUKAfix denture resin (2.34 ± 0.44). Repair with LUKAfix denture resin resulted inferior transverse and impact strength as compared to heat polymerized PMMA resin.


Encouraging Young Pediatric Surgeons and Evaluation of the Effectiveness of a Pediatric Endosurgery Workshop by Self-Assessment and an Objective Skill Validation System.
Background: Japanese pediatric endosurgery experts conducted a workshop for young pediatric surgeons in Russia in collaboration with Russian expert pediatric surgeons. This study was aimed to develop a contributive workshop program and evaluate its impact on young pediatric surgeons. Methods: A 2-day pediatric endosurgery workshop was held in Moscow in February 2020. After conducting a needs assessment survey, Japanese and Russian faculties developed the workshop contents, including pre- and postworkshop skills assessments, lectures, and hands-on training. Skills assessments were performed using the objective skill validation system, the "A-Lap Mini," mimicking intestinal anastomosis. The trainees self-evaluated their knowledge and skills using a five-point scale. Results: Fifteen novice trainee participated and 14 (93.3%) completed the workshop program. The completion rate for the suturing task before and after the workshop was 40.0% (6/15) and 85.7% (12/14), respectively. The following five skill evaluation criteria, which were objectively evaluated: performance time changed from 751.6 ± 247.1 seconds to 780.0 ± 313.3 seconds (P > .05), number of full-thickness sutures improved from 1.0 ± 1.41 to 2.64 ± 0.84 (P = .003), area of wound-opening changed from 0.42 ± 0.83 mm2 to 0.53 ± 1.13 mm2 (P > .05), suture tension improved from 55.48% ± 19.51% to 61.95% ± 23.91% (P > .05), and maximum air leakage pressure improved from 3.76 ± 2.11 kPa to 8.42 ± 7.68 kPa (P > .05). Regarding the self-assessed questionnaire administered before and after the workshop, the confidence in endosurgery skills significantly improved as follows: forceps manipulation ability improved from 2.7 to 3.7 (P < .05), and suturing performance improved from 2.5 to 3.6 (P < .05). The usefulness of the workshop for clinical surgery was scored at 4.3. Conclusions: Quantitative skill evaluation with an automatic feedback function was useful for endosurgery training. Delivering feedback concerning the assessment results to the trainee helps them to determine the specific training requirements needed for clinical endosurgery.


Coordinated Target Tracking via a Hybrid Optimization Approach.
Recent advances in computer science and electronics have greatly expanded the capabilities of unmanned aerial vehicles (UAV) in both defense and civil applications, such as moving ground object tracking. Due to the uncertainties of the application environments and objects' motion, it is difficult to maintain the tracked object always within the sensor coverage area by using a single UAV. Hence, it is necessary to deploy a group of UAVs to improve the robustness of the tracking. This paper investigates the problem of tracking ground moving objects with a group of UAVs using gimbaled sensors under flight dynamic and collision-free constraints. The optimal cooperative tracking path planning problem is solved using an evolutionary optimization technique based on the framework of chemical reaction optimization (CRO). The efficiency of the proposed method was demonstrated through a series of comparative simulations. The results show that the cooperative tracking paths determined by the newly developed method allows for longer sensor coverage time under flight dynamic restrictions and safety conditions.


Potencies and selectivities of inhibitors of acetylcholinesterase and its molecular forms in normal and Alzheimer's disease brain.
Eight inhibitors of acetylcholinesterase (AChE), tacrine, bis-tacrine, donepezil, rivastigmine, galantamine, heptyl-physostigmine, TAK-147 and metrifonate, were compared with regard to their effects on AChE and butyrylcholinesterase (BuChE) in normal human brain cortex. Additionally, the IC50 values of different molecular forms of AChE (monomeric, G1, and tetrameric, G4) were determined in the cerebral cortex in both normal and Alzheimer's human brains. The most selective AChE inhibitors, in decreasing sequence, were in order: TAK-147, donepezil and galantamine. For BuChE, the most specific was rivastigmine. However, none of these inhibitors was absolutely specific for AChE or BuChE. Among these inhibitors, tacrine, bis-tacrine, TAK-147, metrifonate and galantamine inhibited both the G1 and G4 AChE forms equally well. Interestingly, the AChE molecular forms in Alzheimer samples were more sensitive to some of the inhibitors as compared with the normal samples. Only one inhibitor, rivastigmine, displayed preferential inhibition for the G1 form of AChE. We conclude that a molecular form-specific inhibitor may have therapeutic applications in inhibiting the G1 form, which is relatively unchanged in Alzheimer's brain.


The ecumenical and non-ecumenical dialectic of Christian bioethics.
Non-ecumenical Christian bioethics will seem a strange category for many. The category relies on the recognition that bioethics mediates morality and ethics in healthcare. As such bioethics will have particular content. It is the content of a moral vision that both divides and unites. The enterprise of non-ecumenical Christian bioethics explores how Christians are both divided and united on the issue of bioethics. Non-ecumenical Christian bioethics is opposed to a facile ecumenism that reduces the content of Christian morality to the lowest common denominator.


Plasma lipoproteins are important components of the immune system.
Plasma lipoproteins (VLDL, LDL, Lp[a] and HDL) function primarily in lipid transport among tissues and organs. However, cumulative evidence suggests that lipoproteins may also prevent bacterial, viral and parasitic infections and are therefore a component of innate immunity. Lipoproteins can also detoxify lipopolysaccharide and lipoteichoic acid. Infections can induce oxidation of LDL, and oxLDL in turn plays important anti-infective roles and protects against endotoxin-induced tissue damage. There is also evidence that apo(a) is protective against pathogens. Taken together, the evidence suggests that it might be valuable to introduce the concept that plasma lipoproteins belong in the realm of host immune response.


Cavitation inception from bubble nuclei.
The tensile strength of ordinary water such as tap water or seawater is typically well below 1 bar. It is governed by cavitation nuclei in the water, not by the tensile strength of the water itself, which is extremely high. Different models of the nuclei have been suggested over the years, and experimental investigations of bubbles and cavitation inception have been presented. These results suggest that cavitation nuclei in equilibrium are gaseous voids in the water, stabilized by a skin which allows diffusion balance between gas inside the void and gas in solution in the surrounding liquid. The cavitation nuclei may be free gas bubbles in the bulk of water, or interfacial gaseous voids located on the surface of particles in the water, or on bounding walls. The tensile strength of these nuclei depends not only on the water quality but also on the pressure-time history of the water. A recent model and associated experiments throw new light on the effects of transient pressures on the tensile strength of water, which may be notably reduced or increased by such pressure changes.


Tachykinin-induced anion secretion in guinea pig distal colon: role of neural and inflammatory mediators.
The effects of substance P and related tachykinins on short-circuit current were determined in submucosa-mucosa sheets of guinea pig distal colon. Substance P, neurokinin A, eledoisin and physalaemin evoked a concentration-dependent increase in short-circuit current with a rank order of potencies of substance P = physalaemin greater than eledoisin = neurokinin A. The substance P response was reduced in chloride-free solutions or after addition of furosemide. Tetrodotoxin, atropine, mecamylamine and pyrilamine reduced the response to substance P. The substance P antagonist, [D-Arg1,D-Phe5,Trp7,9,Leu11]-substance P, reduced the response to neural stimulation and to exogenous substance P. The results suggest that substance P evokes anion secretion by activating cholinergic and noncholinergic neurons and by releasing histamine.


Efficient Electrocatalysis for the Preparation of (Hetero)aryl Chlorides and Vinyl Chloride with 1,2-Dichloroethane.
Although the application of 1,2-dichloroethane (DCE) as a chlorinating reagent in organic synthesis with the concomitant release of vinyl chloride as a useful byproduct is a fantastic idea, it still presents a tremendous challenge and has not yet been achieved because of the harsh dehydrochlorination conditions and the sluggish C-H chlorination process. Here we report a bifunctional electrocatalysis strategy for the catalytic dehydrochlorination of DCE at the cathode simultaneously with anodic oxidative aromatic chlorination using the released HCl as the chloride source for the efficient synthesis of value-added (hetero)aryl chlorides. The mildness and practicality of the protocol was further demonstrated by the efficient late-stage chlorination of bioactive molecules.


Ubiquitination of the ubiquitin-binding machinery: how early ESCRT components are controlled.
To be able to quickly and accurately respond to the environment, cells need to tightly control the amount and localization of plasma membrane proteins. The post-translation modification by the protein modifier ubiquitin is the key signal for guiding membrane-associated cargo to the lysosome/vacuole for their degradation. The machinery responsible for such sorting contains several subunits that function as ubiquitin receptors, many of which are themselves subjected to ubiquitination. This review will focus on what is currently known about the modulation of the machinery itself by ubiquitination and how this might affect its function with a special emphasis on current findings from the plant field.


Association between the appendix and the fecalith in adults.
We sought to determine the association between the presence of a fecalith and acute/nonperforated appendicitis, gangrenous/perforated appendicitis and the healthy appendix. We retrospectively analyzed appendectomies performed between October 2003 and February 2012. We collected data on age, sex, appendix histology and the presence of a fecalith. During the study period, 1357 appendectomies were performed. Fecaliths were present in 186 patients (13.7%). There were 94 male (50.5%) and 92 female patients, and the mean age was 32 (range of 10-76) years. The fecalith rate was 13%- 16% and was nonexistant after age 80 years. The main groups with fecaliths were those with acute/nonperforated appendicitis (n = 121, 65.1%, p = 0.041) and those with a healthy appendix (n = 65, 34.9%, p = 0.003). The presence of fecaliths in the gangrenous/perforated appendicitis group was not significant (n = 19, 10.2%, p = 0.93). There were no fecaliths in patients with serositis, carcinoid or carcinoma. Our data confirm the theory of a statistical association between the presence of a fecalith and acute (nonperforated) appendicitis in adults. There was also a significant association between the healthy appendix and asymptomatic fecaliths. There was no correlation between a gangrenous/perforated appendix and the presence of a fecalith. The fecalith is an incidental finding and not always the primary cause of acute (nonperforated) appendictis or gangrenous (perforated) appendicitis. Further research on the topic is recommended.


Seroprevalence of dengue infection in the municipalities of Armenia, Calarcá, La Tebaida and Montenegro in Quindío, 2014.
Dengue is a serious public health problem in Colombia; it is prevalent in 90% of the municipalities in Quindío. Studies on its seroprevalence are required to address public health interventions. To establish the seroprevalence of dengue infection in neighborhoods with high incidence in the municipalities of Armenia, Calarcá, La Tebaida and Montenegro, Quindío, in 2014. We conducted a probabilistic, stratified, two-stage prevalence study. We interviewed 658 residents in the urban area of the selected municipalities. After they signed the informed consent, we took a blood sample to determine dengue IgG and IgM antibodies. Seroprevalence of IgG in Quindío was 89,4%; in Armenia it was 88,7%, in Calarcá, 81,5%, in Montenegro, 91,8% and in La Tebaida 97,8%. IgM was 14, 2% in Quindío; in Armenia it was 11,5%, in Calarcá, 13,0%, in Montenegro, 13,1% and in La Tebaida, 28,9%. We found a high prevalence of both IgG and IgM in the four municipalities. We had positive results for IgM in all age groups, which suggests recent infection. We also found simultaneous seropositivity for IgG and IgM (12.9%), which may indicate infection by another serotype or presence of infection in the past three months. A multisectoral approach is necessary for dengue control in Quindío.


[Postpartum hemmorhage: prevention and treatment by arterial embolization and activated recombinant factor VII].
Primary postpartum hemorrhage occurs in 5% of deliveries and is source of serious maternal morbidity. Active management of third stage of labor with oxytocin administration reduces the risk by more than 60%. Hemorrhage is always underestimated. Teamwork with all involved caregivers is necessary. In case of failure or primary care, such as uterine massage, uterotonics and revision of uterus, cervix and vagina, two treatments must be offered to women: arterial embolization and activated recombinant factor VII. Embolization is effective in 75-100% of cases, thus avoiding hysterectomy. When possible, transfer to a center offering embolization shoud be decided early.


Effects of organic matrix proteins on the interfacial structure at the bone-biocompatible nacre interface in vitro.
The biocompatibility and potential osteoinductivity of nacre have favored its use as a bone-grafting material. The present study is to investigate the interfacial structure at the bone-nacre interface resulting from organic matrix proteins, which emphasizes the mechanism of bone-bonding ability and biocompatibility of the shell tissues such as nacre and biogenic calcite. To understand the interfacial reaction, the zeta potential measurements, provide for a unique method to quantify the actual state of the interface in situ, were used for synthetic and biogenic calcium carbonate suspensions with respect to pH and the organic matrix as an additive. The zeta potentials and surface charge density show that the organic matrix proteins are main charge regulators, resulting in the stabilized tissue properties as compared with synthetic crystals. Also, in forming calcium carbonate crystals with the additives, the conformation of organic matrix has an important role in the understanding of the newly formed interfacial structure. The result provides the primary role of the organic matrix proteins in controlling the formation of interfacial structure and biocompatibility with bone as well as the stability of biogenic tissues. And it gives a new insight into the usefulness of zeta potential measurement to describe the in vivo interaction between the bone and implants.


[The role of CXC and CC chemokines in patients with uveal melanoma].
Uveal melanoma is a malignant neoplasm with high metastatic potential; its pathogenesis is currently being studied. Chemokines play a key role not only in the inflammatory response, but also in enhancing angiogenesis, tumor invasiveness, increasing proliferative potential and metastasis. To study the role of chemokines of classes CXC and CC in blood serum and tear fluid of patients with uveal melanoma. The study included 118 people aged 53.7±12.2 years, among them 80 patients with uveal melanoma and 38 healthy donors. Group 1 included 32 patients with small tumors, group 2 (medium-sized tumors) - 26 patients; group 3 (large tumors) was comprised of 22 patients. Chemokines of classes CC (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL11/Eotaxin) and CXC (CXCL1/GRO-α, CXCL8/IL-8, CXCL10/IP-10, CXCL12/SDF-1α) were determined by multiplex analysis of the blood serum and tear fluid. Statistical processing: Student's t-test, Fisher criteria, and Pierson's chi-squared test (χ2), differences were considered significant at p<0.05. Significantly increased level of chemokines with pro-inflammatory (CCL5/RANTES), proliferative (CXCL10/IP-10) and pro-angiogenic (CXCL12/SDF-1α) effects was found in the blood serum of patients with small-sized uveal melanoma in comparison with healthy donors. Concentration of all studied pro-inflammatory, proliferative, and pro-angiogenic chemokines in the lacrimal fluid was found to be significantly elevated in both the affected and the paired "healthy" eyes in all 3 groups of patients, with the maximum content seen in the large tumor group. The obtained data indicates that early local and systemic immune imbalance can be observed in uveal melanoma, and detection of chemokines can serve as a good reason for developing targeted therapy for small uveal melanoma.


Most children who are allergic to cow's milk tolerate yogurt.
Cow's milk allergy is the most common food allergy in childhood. Changes occur in the protein structure of milk during yogurt fermentation. This study aimed to determine whether children who are diagnosed with a cow's milk allergy can tolerate yogurt. We performed a yogurt challenge test on 34 children who were diagnosed with a cow's milk allergy in our Pediatric Allergy Outpatient Clinic. The mean age of 24 male and 10 female children was 24 ± 13 months. A reaction was observed in 17 (50%) patients, whereas no reaction was observed in the other 17 (50%) during an oral yogurt challenge test that was performed in all of the 34 patients with a cow's milk allergy. Cow's milk-specific immunoglobulin E levels were significantly lower in the group of children who could tolerate yogurt than in the group of children who could not tolerate yogurt. Yogurt is tolerated by half of children with a cow's milk allergy when subjected to a challenge test performed with yogurt, which is consumed as much as milk in Turkey.


Synthesis of 18F-Labeled Aryl Fluorosulfates via Nucleophilic Radiofluorination.
Sulfuryl fluoride gas is a key reagent for SO2F transfer. However, conventional SO2F transfer reactions have limited 18F-radiochemistry translation, due to the inaccessibility of gaseous [18F]SO2F2. Herein, we report the first SO2F2-free synthesis of aryl [18F]fluorosulfates from both phenolic and isolated aryl imidazylate precursors with cyclotron-produced 18F-. The radiochemical yields ranged from moderate to good with excellent functional group tolerance. The reliability of our approach was validated by the automated radiosynthesis of 4-acetamidophenyl [18F]fluorosulfate.


Automated Detection of Privacy Sensitive Conditions in C-CDAs: Security Labeling Services at the Department of Veterans Affairs.
Care coordination across healthcare organizations depends upon health information exchange. Various policies and laws govern permissible exchange, particularly when the information includes privacy sensitive conditions. The Department of Veterans Affairs (VA) privacy policy has required either blanket consent or manual sensitivity review prior to exchanging any health information. The VA experience has been an expensive, administratively demanding burden on staffand Veterans alike, particularly for patients without privacy sensitive conditions. Until recently, automatic sensitivity determination has not been feasible. This paper proposes a policy-driven algorithmic approach (Security Labeling Service or SLS) to health information exchange that automatically detects the presence or absence of specific privacy sensitive conditions and then, to only require a Veteran signed consent for release when actually present. The SLS was applied successfully to a sample of real patient Consolidated-Clinical Document Architecture(C-CDA) documents. The SLS identified standard terminology codes by both parsing structured entries and analyzing textual information using Natural Language Processing (NLP).


The Internet's effect on personality traits: An important casualty of the "Internet addiction" paradigm.
Background and aims The "Internet addiction" paradigm has been criticized for several shortcomings, including inattention to specific online behaviors, not distinguishing the Internet from other media, insufficient focus on comorbidities, and definitions that do not take into account the constant access now possible. The paradigm's biggest casualty, however, may be that it has diverted attention away from subtle personality changes that seem to occur online, including in users who cannot be considered "addicted" under any definition. Methods A narrative assessment of the literature was conducted, focusing on the Internet's effects on personality traits as revealed in studies of Internet users. Results Impulsivity, narcissism, and aggression are some of the personality traits that seem to be nurtured by the Internet, with possible negative offline consequences. Discussion Ignoring the Internet's subtle effects on personality as we embrace an addiction model that implies severe pathology makes the majority of Internet users feel deceptively immune to the psychological effects of new technologies. It also limits our understanding of the big cultural shifts that are happening as a result. Conclusion The Internet's potentially negative effect on personality, and by extension on society at large, is a fundamental part of online psychology, one well worthy of further investigation.


[Epididymal cyst in von Hippel-Lindau syndrome: clinicopathologic analysis of 3 cases].
To investigate the clinicopathologic features of epididymal cyst in von Hippel-Lindau (VHL) syndrome. We reviewed the clinical data of 3 epididymal cyst patients treated by surgery, and detected the expressions of HIF-1alpha, VEGF, alpha-SMA and CD34 in the epididymal tissue samples by the immunohistochemistry SP method. All the 3 patients underwent surgical removal of the epididymal cyst. Immunohistochemistry of the epididymal tissues showed HIF-1alpha, VEGF, alpha-SMA and CD34 to be positive. All the 3 cases were confirmed to be VHL syndrome, 1 right after surgery, and the other 2 within 8 years postoperatively. Epididymal cyst is a usual benign disease, which may occur independently of or be complicated by VHL syndrome. If immunohistochemistry of epididymal tissues shows HIF-1alpha, VEGF, alpha-SMA and CD34 to be positive, VHL syndrome should be considered, and further clinical examinations and post-operation follow-up are necessitated.


Molecular epidemiology of dengue 2 viruses in the Philippines: genotype shift and local evolution.
The pre-membrane (prM) and envelope (E) genes of 41 viruses isolated from dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) patients from 1995 to 2002 were sequenced to determine the genetic variability of dengue 2 (DENV 2) viruses in the Philippines. The envelope sequence data were compared with a global sample of DENV 2 obtained from GenBank. Phylogenetic analysis revealed that two distinct genotypes, Asian 2 and Cosmopolitan, are currently circulating locally, each with the potential to cause severe hemorrhagic disease. After the initial isolation in 1998, the Cosmopolitan genotype has gradually and effectively replaced Asian genotype 2 in the Philippines. Members of this genotype were closely related to viruses from Australia, Singapore, and Thailand.


Base rates of negative response bias and malingered neurocognitive dysfunction among criminal defendants referred for neuropsychological evaluation.
Several studies reveal the prevalence of negative response bias (NRB) in civil forensic settings, but little NRB base rate information is available for criminal forensic neuropsychological settings. We reviewed the published literature on neuropsychological NRB in the civil setting. We then present data from 105 criminal defendants serially referred for neuropsychological assessment to determine the prevalence of NRB. The rate of NRB using one positive indicator was 89.5%. The rate was 70.5% when using two or more positive indicators and 53.3% for three or more indicators. Based on the Slick, Sherman, and Iverson (1999) classification for malingered neurocognitive dysfunction (MND), 19% were Valid, 26.7% were Possible MND, 32.4% were Probable MND, and 21.9% were Definite MND. The combined rate of probable and definite MND was 54.3%. Results suggest rates of neuropsychological NRB and malingering in criminal forensic settings are higher than in civil forensic settings.


Incorporating repeating temporal association rules in Naïve Bayes classifiers for coronary heart disease diagnosis.
In this paper, we develop a Naïve Bayes classification model integrated with temporal association rules (TARs). A temporal pattern mining algorithm is used to detect TARs by identifying the most frequent temporal relationships among the derived basic temporal abstractions (TA). We develop and compare three classifiers that use as features the most frequent TARs as follows: (i) representing the most frequent TARs detected within the target class ('Disease = Present'), (ii) representing the most frequent TARs from both classes ('Disease = Present', 'Disease = Absent'), (iii) representing the most frequent TARs, after removing the ones that are low-risk predictors for the disease. These classifiers incorporate the horizontal support of TARs, which defines the number of times that a particular temporal pattern is found in some patient's record, as their features. All of the developed classifiers are applied for diagnosis of coronary heart disease (CHD) using a longitudinal dataset. We compare two ways of feature representation, using horizontal support or the mean duration of each TAR, on a single patient. The results obtained from this comparison show that the horizontal support representation outperforms the mean duration. The main effort of our research is to demonstrate that where long time periods are of significance in some medical domain, such as the CHD domain, the detection of the repeated occurrences of the most frequent TARs can yield better performances. We compared the classifier that uses the horizontal support representation and has the best performance with a Baseline Classifier which uses the binary representation of the most frequent TARs. The results obtained illustrate the comparatively high performance of the classifier representing the horizontal support, over the Baseline Classifier.


Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009.
Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity [especially visceral], glucose intolerance, endothelial dysfunction), each of which is an independent risk factor for cardiovascular disease (CVD). Multiple prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes, as well as in non-diabetic individuals. The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients. The current epidemic of diabetes is being driven by the obesity epidemic, which represents a state of tissue fat overload. Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with thiazolidinediones mobilises fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Insulin resistance and lipotoxicity represent the missing links (beyond the classical cardiovascular risk factors) that help explain the accelerated rate of CVD in type 2 diabetic patients.


Brain Perfusion Impairment in Neurologically Asymptomatic Adult Patients with Sickle-Cell Disease Shown by Voxel-Based Analysis of SPECT Images.
Cerebrovascular lesions are frequently observed in patients with sickle-cell disease (SCD) and these structural lesions are preceded by insidious perfusion deficits. Our aim was to investigate the presence of brain perfusion deficits in neurologically asymptomatic SCD patients, especially affecting microvessels. For this study, 42 SCD patients [33 sickle-cell anemia (HbSS), 6 sickle hemoglobin C disease (HbSC), and 3 sickle β-thalassemia disease (HbSβ)] with mean hematocrit of 25.1 (±4.85; 15.6-38.5) underwent brain perfusion single photon emission computerized tomography (SPECT) using the tracer (99m)Tc-ECD. Images from SCD patients were compared to images of a healthy control group (29 females and 20 males, mean age 31 ± 8; range 25-49 years). Images underwent voxel-wise comparison of regional tracer uptake using paired t-test to estimate the probability of each voxel to have an increased or decreased tracer uptake. When compared to controls, SCD patients exhibited significantly reduced tracer uptake in basal ganglia and thalami, the anterior frontal region and the watershed region of the temporo-parietal-occipital transition (p < 0.05). Our study showed that neurologically asymptomatic adult SCD patients exhibit a pattern of reduced (99m)Tc-ECD tracer uptake demonstrated by SPECT. Early diagnosis of this cerebral vasculopathy has prognostic implications and can be determinant in considering therapeutic alternatives to avoid increasing brain lesion load and progressive disability.


Direct Invasion of the Optic Nerves, Chiasm, and Tracts by Cryptococcus neoformans in an Immunocompetent Host.
Cryptococcus spp is a common fungal infection and frequent cause of meningitis in immunocompromised patients; however, immunocompetent patients are also at risk of infection. Visual loss often occurs via elevated intracranial hypertension but can rarely occur through direct optic nerve, chiasm, or tract invasion. We report a case of a 38-year-old woman who presented with decreased acuity in both eyes. She had generalized visual field constriction in the right eye and temporal hemianopsia in the left eye. Magnetic resonance imaging of the brain and orbits showed multiple areas of ill-defined enhancement in the optic chiasm and tracts as well as in the diaphragmatic sella, prepontine and interpeduncular cisterns, and along cranial nerves VI, VII, and VIII bilaterally. Initial cerebrospinal fluid (CSF) showed 34 white blood cells, hypoglycorrhachia, and negative cryptococcal antigen and bacterial and fungal cultures. A transphenoidal biopsy of the dura and pituitary gland was unremarkable. Empiric steroids resulted in marked improvement in visual acuity in both eyes, but while tapering steroids, she developed rapid visual loss bilaterally. Repeat CSF performed 6 weeks later demonstrated a cryptococcal antigen titer of 1:512. Retroactive staining of the pituitary biopsy was positive for mucicarmine, a component of the polysaccharide capsule of Cryptococcus spp. After induction therapy with amphotericin B and flucytosine and 1 year of fluconazole, her visual acuity was 20/20 in both eyes. In summary, Cryptococcus can affect immunocompetent patients and often presents with insidious, chronic meningitis. Visual loss is common in cryptococcal meningitis but usually results from fulminant papilledema related to elevated intracranial pressure. In rare cases, direct nerve or chiasm infiltration by the fungus results in vision loss.


Downward gaze palsy caused by bilateral lesions of the rostral mesencephalon.
A 55-year-old man with diabetes mellitus developed diplopia and experienced difficulty in moving his eyes in the vertical plane, especially downward. Horizontal movement of each eye was normal with exotropia. Magnetic resonance imaging revealed small and high signals on both sides of the midbrain near the interstitial nucleus of Cajal (INC). Based upon the recent experimental evidence, we speculate that bilateral lesions involving the INC may have caused downward gaze palsy in our patient.


Aortic sinus of Valsalva aneurysms simulating primary right-sided valvular heart disease.
While acute regurgitation is the most common valvular lesion associated with aortic sinus of Valsalva aneurysms, this report describes the pathological findings in five patients in whom primary right-sided valve dysfunction was simulated by sinus of Valsalva aneurysms. In two patients aneurysms of the noncoronary sinus projected into the right atrium at the level of the tricuspid valve and caused tricuspid incomptence. In three patients aneurysms of the right sinus of Valsalva projected into the right ventricle immediately below the pulmonic valve and caused pulmonary outflow tract obstruction. In only one of these patients was the aneurysm perforated at necropsy. Although valvular dysfunction was evident clinically, in none was there a clinical suspicion of a sinus of Valsalva aneurysm. In addition to valvular dysfunction, two patients had conduction disturbances and two, right coronary arterial occlusions found to be the result of aneurysms. The risks of valve dysfunction, arrythmias, aneurysm rupture, and sudden death and the ability to correct this lesion surgically make it especially important to consider aortic sinus of Valsalva aneurysm as a cause of obscure right-sided valvular disease.


Effect of interleukin-4 on the growth of granulocyte-macrophage progenitor cells stimulated by hematopoietic growth factors.
The effects of recombinant murine interleukin-4 (rmIL-4) on murine granulocyte-macrophage progenitor cells (CFU-GM) were investigated in the presence or absence of recombinant human granulocyte colony stimulating factor (rhG-CSF), recombinant murine granulocyte-macrophage colony stimulating factor (rmGM-CSF) or recombinant murine interleukin-3 (rmIL-3) both in serum-free and serum-containing cultures. IL-4 alone could not support any CFU-GM colony formation in both culture systems. In serum-free cultures, IL-4 inhibited CFU-GM colony formation stimulated by G-CSF, GM-CSF or IL-3 from whole bone marrow cells (whole BM cells), nonadherent, nonphagocytic and T cell-depleted BM cells (fractionated BM cells) or whole BM cells of 5-Fluorouracil (5-FU) treated mice. On the other hand, in serum-containing cultures, IL-4 inhibited CFU-GM colony formation stimulated by GM-CSF or IL-3, but IL-4 dose-dependently enhanced G-CSF-stimulated colony formation from both whole and fractionated BM cells. Morphological examinations revealed that IL-4 predominantly inhibited granulocyte-lineage colony formation stimulated by GM-CSF or IL-3 in both culture systems. When combined with G-CSF, IL-4 predominantly inhibited granulocyte-lineage colony formation and relatively increased macrophage-lineage colonies, but in serum-containing culture, IL-4 significantly increased macrophage-lineage colony formation. The results of the present study suggest that IL-4 has an inhibitory effect on the factors (G-CSF, GM-CSF, IL-3)-dependent CFU-GM colony formation in serum-free condition and enhances only G-CSF-stimulated CFU-GM colony formation in serum-containing condition.


Recreational drug use and suicidality among Italian young adults.
The aim of the study was to explore recreational drug use patterns among a sample of Italian young adults and to examine the role of substance misuse on suicidality. Three hundred and forty Italian young adults between 19 and 30 years of age completed measures of suicidality (Reasons for Living Inventory, Beck Hopelessness Scale, and Suicide Score Scale), depression (Zung Depression Scale), problem drinking (Michigan Alcohol Screening Test), and drug use (Drug Abuse Screening Test). Respondents were classified as problem drug users and drinkers (14.7% and 24.1%, respectively), and men were overrepresented in both groups. Alcohol and drugs misuse was significantly associated with reasons for living, hopelessness, suicidal attitudes, and depression. A multiple regression analysis resulted in four models predictive of suicide risk and four predictors were extracted--the Drug Abuse Screening Test, the Zung Depression Scale, and Loss of Motivation as positive predictors of suicide risk with Survival and Coping Beliefs as negative predictors.


[Development of high sensitivity immunochromatographic test card for zearalenone].
To develop a highly sensitive immunochromatographic test card for zearalenone. Gold nanoflowers(AuNFs) with a particle size of(116. 7±2. 0) nm and multiple branches was prepared and labeled to the zearalenone monoclonal antibody. Based on the gold nanoflower-labeled zearalenone monoclonal antibody(AuNF-ZEN-Mab), a zearalenone gold nanoflower immunochromatographic test card(ZEN-GFICT) was developed for the detection of food and feed. The detection sensitivities of ZEN-GFICT(contrast method) and(cancellation method) for ZEN standards were 0. 5 and 6 ng/mL, respectively, and the limit of detection(LOD) for actual samples were 5 and 60 μg/kg, respectively. It was 6 times(contrast method) and 4. 5 times(cancellation method) of the traditional ZEN nano gold immunochromatographic test card(ZEN-GICT). The total conformity of the ZEN-GFICT judgment result(contrast method and cancellation method) of 21 samples compared with those of the ELISA kit were 90. 5% and 90. 5%, respectively. The ZEN content in the sample with three intervals of less than 5 μg/kg, 5-60 μg/kg and more than 60 μg/kg could be screened by the ZEN-GFICT contrast method and the cancellation method. It is possible to screen samples with a low degree of ZEN contamination.


Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers.
Diagnosing early myocardial ischemia (the initial 4 to 6 h after interruption of blood flow to part of the myocardium) remains a challenge for clinical and forensic pathologists. Several immunohistochemical markers have been proposed for improving postmortem detection of early myocardial ischemia; however, no single marker appears to be both sufficiently specific as well as sensitive. This review summarizes the diverse categories of molecular tissue markers that have been investigated in human autopsy samples with acute myocardial infarction as well as in the well-established and widely used in vivo animal model of early myocardial ischemia (permanent ligation of the coronary artery). Recently identified markers appearing during the initial 2 h of myocardial ischemia are highlighted. Among them, only six were tested for specificity (C5b-9, hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, heart fatty acid binding protein, connexin 43, and JunB). Despite the discovery of several potentially promising markers (in terms of early expression and specificity), many of them remain to be tested and validated for application in routine diagnostics in clinical and forensic pathology. In particular, research investigating the postmortem stability of these markers is required before any might be implemented into routine diagnostics. Establishing a standardized panel of immunohistochemical markers may be more useful for improving sensitivity and specificity than searching for a single marker.


Taxonomy of the Rhizopogon vinicolor species complex based on analysis of ITS sequences and microsatellite loci.
We are re-addressing species concepts in the Rhizopogon vinicolor species complex (Boletales, Basidiomycota) using sequence data from the internal-transcribed spacer (ITS) region of the nuclear ribosomal repeat, as well as genotypic data from five microsatellite loci. The R. vinicolor species complex by our definition includes, but is not limited to, collections referred to as R. vinicolor Smith, R. diabolicus Smith, R. ochraceisporus Smith, R. parvulus Smith or R. vesiculosus Smith. Holo- and/or paratype material for the named species is included. Analyses of both ITS sequences and microsatellite loci separate collections of the R. vinicolor species complex into two distinct clades or clusters, suggestive of two biological species that subsequently are referred to as R. vinicolor sensu Kretzer et al and R. vesiculosus sensu Kretzer et al. Choice of the latter names, as well as morphological characters, are discussed.


[Clinical study of pulmonary infection in kidney transplantation recipients taking new immunosuppressant].
To explore the etiopathogenesis, therapy and incidence of pulmonary infection in kidney transplantation recipients taking new immunosuppressant. The clinical data from 752 kidney transplant recipients were retrospectively analyzed, who were divided into 3 groups according to the immunosuppressants administered, namely group A (CsA+MMF+Pred, n=226), group B (FK506+MMF+Pred, n=386) and group C (FK506+Rap+Pred, n=140). The incidence and mortality of pulmonary infection were recorded and the analysis of etiopathogenesis, diagnosis and therapy of pulmonary infection were carried out in the 3 groups. Fifty-three patients acquired post-transplant pulmonary infection. The incidence of pulmonary infection was 7.08% (16/226) in group A, 7.25% (28/386) in group B and 6.43% (9/140) in group C. One patient died in group A and 2 in group B. Among the 53 patients, 24 had simple bacterial infection, 9 had cytomegalovirus infection, 1 had mycotic infection, 17 had combined infection, and 2 had unidentified pathogen infection. Of the pathogenic bacteria detected, 68.35% were Gram-negative. Gram-negative bacteria are most likely responsible for pulmonary infection after kidney transplantation, which most possibly occurs within 6 months after kidney transplantation. Early diagnosis and early treatment are critical for decreasing the mortality of severe pneumonia and for improving the survival rate of the patients and grafts.


Sorafenib Versus Apatinib Both Combined Transarterial Chemoembolization for Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis: A Comparative Retrospective Study.
To compare the efficacy and safety of transarterial chemoembolization (TACE) combining with sorafenib or apatinib for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). From June 2015 to March 2020, a total of 89 consecutive advanced HCC patients with PVTT who were treated with sorafenib-TACE (S-TACE) or apatinib-TACE (A-TACE) in our center were enrolled. The overall survival (OS), time to progression (TTP), tumor response, and adverse events in the two groups were compared. There were 32 and 41 patients included in the S-TACE group and A-TACE group, respectively. The median follow-up was 10.0 months (range, 3.0-36.0 months) in the whole study. The median OS (11.0 vs. 10.0 months, P = 0.419), median TTP (5.0 vs. 6.0 months, P = 0.073), and tumor response (P = 0.529) between the S-TACE group and the A-TACE group were not significantly different. The adverse events related to sorafenib or apatinib were tolerable. S-TACE and A-TACE exhibited comparable prognosis for HCC patients with PVTT, which provide another effective and safe method of A-TACE for these patients except for conventional S-TACE.


Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced S-phase entry.
Deregulation of the retinoblastoma protein (pRB) pathway is a hallmark of cancer. In the absence of other genetic alterations, this deregulation results in lack of differentiation, hyperproliferation and apoptosis. The pRB protein acts as a transcriptional repressor by targeting the E2F transcription factors, whose functions are required for entry into S phase. Increased E2F activity can induce S phase in quiescent cells--this is a central element of most models for the development of cancer. We show that although E2F1 alone is not sufficient to induce S phase in diploid mouse and human fibroblasts, increased E2F1 activity can result in S-phase entry in diploid fibroblasts in which the p53-mediated G1 checkpoint is suppressed. In addition, we show that E2F1 can induce S phase in primary mouse fibroblasts lacking pRB. These results indicate that, in addition to acting as an E2F-dependent transcriptional repressor, pRB is also required for the cells to retain the G1 checkpoint in response to unprogrammed proliferative signals.


[Absence of HTLV-I/II virus circulation in blood donors from the provinces of Santa Fe and Santiago del Estero].
In the present study, we evaluated the seroprevalence of HTLV-I/II infection among the blood donors in Santa Fe and Santiago del Estero provinces. A total of 1327 serum samples from blood donors from Rafaela blood bank of Santa Fe province and 3382 serum samples from blood donors from Dr Edgar Bouzon blood bank of Santiago del Estero province were studied. The antibody screening was done by particle agglutination assay (PA) (SERODIA, Fujirebio Inc., Tokyo, Japan) or by enzyme immuno assay (EIA) (Abbott HTLV-I/HTLV-II EIA, Abbott, Germany). The "in house" indirect immunofluorescence assay (IFA) and Western blot (Bioblot HTLV Biokit, Barcelona, Spain) were used as confirmatory assays. All the samples resulted negative for specific antibodies against HTLV-I/II. These results suggest that HTLV-I/II are not circulating in low risk populations in these provinces or that the prevalences of infection would be lower than that reported by blood banks in other provinces of Argentina.


Effect of aromatic carcinogens and noncarcinogenic analogs on the induction of murine alpha/beta interferon.
The effects of several aromatic carcinogens and their noncarcinogenic analogs on the production of alpha/beta interferon by mouse embryo fibroblasts were determined. The carcinogens 2-naphthylamine and 9,10-dimethylanthracene significantly depressed alpha/beta interferon production, while their poorly or noncarcinogenic analogs, 1-naphthylamine and anthracene, respectively, had no significant effect. Neither the carcinogen benzidine nor its poorly carcinogenic analog 3,3',5,5'-tetramethylbenzidine had any effect on alpha/beta interferon production. These data, taken together with previous findings, suggest the possibility of drawing a high correlation between the carcinogenic potential of a chemical and its effect on interferon production.


The use of pegorgotein in the treatment of frostbite.
Free oxygen radicals have been postulated to be an important mediator of injury in frostbite. A long-acting version of the endogenous scavenger enzyme, superoxide dismutase, has been created by conjugating it with polyethylene glycol (pegorgotein, formerly known as PEG-SOD). This study evaluated the efficacy of pegorgotein on frostbite tissue survival when administered prior to rewarming. In a prospective study, two groups of nine rabbits received a standardized frostbite injury using a modified Weatherley-White model. A control group received no pharmacologic therapy; the treatment group received 10,000 IU/kg pegorgotein intravenously immediately postinjury. Healing was followed until a clear line of demarcation was apparent (10 days). The percentage of viable ear surface remaining at the end of the study was measured and used to compare the effectiveness of treatment. Student's t-test was used to determine statistical significance. The study was designed to have an 80% ability to detect a 35% difference in tissue survival. No significant difference in frostbite injury (p = 0.967) was observed between the control and treatment groups. The treatment group showed a 9.3 +/- 15.5% tissue survival, whereas the control group had 9.6 +/- 14.5% tissue survival. These results indicate no significant treatment effect for pegorgotein on tissue survival in a rabbit frostbite injury model when administered immediately postinjury.


[Comparative analysis of the changing pattern of thyroid disease in patients with type 2 diabetes mellitus in the Perm region after 10 years].
To comparatively analyze thyroid abnormalities in patients with type 2 diabetes mellitus (DM2) in the past 10 years. The thyroid state 10 years ago and presently was evaluated in 166 and 101 patient with DM2, respectively. The patients underwent in-depth physical examination and thyroid hormone functions were evaluated. The pattern of thyroid disease has changed in the patients with DM2 over a 10-year period. During recent mass and individual iodine deficiency prophylaxis, iodine-deficiency goiter had become substantially less frequent in DM2; the T3/T4 ratio has normalized. The prevalence of nodular goiter has remained unchanged. However, the incidence of autoimmune thyroiditis and hypothyroidism, the subclinical form of the latter in particular, has increased statistically significantly. Hypothyroidism has occurred more often during.treatment with glucose-lowering sulfanilamides than during metformin treatment or combined glucose-lowering therapy. Hypothyroidism was generally recognized untimely in the examinees, in elderly patients in particular: the clinical signs of thyroid disease were regarded as manifestations of DM2. Our preliminary data support other authors' opinion that thyroid insufficiency accelerates the rate of development and progression of vascular complications of DM2. The contrinsular effect of Levothyroxine was not recorded during replacement therapy for thyroid insufficiency. Although the incidence of thyroid abnormality is increasing in patients with DM2 in the world, its causes are yet to be explained. The diagnosis of hypothyroidism in patients with DM2 is commonly untimely. At a follow-up of patients with DM2, it is necessary to systematically monitor thyroid function and to initiate levothyroxine replacement therapy in proper time.


Site-specific attachment of a protein to a carbon nanotube end without loss of protein function.
Establishing a nanobiohybrid device largely relies on the availability of various bioconjugation procedures which allow coupling of biomolecules and inorganic materials. Especially, site-specific coupling of a protein to nanomaterials is highly useful and significant, since it can avoid adversely affecting the protein's function. In this study, we demonstrated a covalent coupling of a protein of interest to the end of carbon nanotubes without affecting protein's function. A modified Staudinger-Bertozzi ligation was utilized to couple a carbon nanotube end with an azide group which is site-specifically incorporated into a protein of interest. We demonstrated that Ca(2+)-sensor protein, calmodulin, can be attached to the end of the nanotubes without affecting the ability to bind to the substrate in a calcium-dependent manner. This procedure can be applied not only to nanotubes, but also to other nanomaterials, and therefore provides a fundamental technique for well-controlled protein conjugation.


'Cleanse or Die': British Naval Hygiene in the Age of Steam, 1840-1900.
This article focuses on the consolidation of naval hygiene practices during the Victorian era, a period of profound medical change that coincided with the fleet's transition from sail to steam. The ironclads of the mid- to late- nineteenth century offered ample opportunities to improve preventive medicine at sea, and surgeons capitalised on new steam technologies to provide cleaner, dryer, and airier surroundings below decks. Such efforts reflected the sanitarian idealism of naval medicine in this period, inherited from the eighteenth-century pioneers of the discipline. Yet, despite the scientific thrust of Victorian naval medicine, with its emphasis on collecting measurements and collating statistics, consensus about the causes of disease eluded practitioners. It proved almost impossible to eradicate sickness at sea, and the enclosed nature of naval vessels showed the limitations - rather than the promise - of attempting to enforce absolute environmental controls. Nonetheless, sanitarian ideology prevailed throughout the steam age, and the hygienic reforms enacted throughout the fleet showed some of the same successes that attended the public health movement on land. It was thus despite shifting ideas about disease and new methods of investigation that naval medicine remained wedded to its sanitarian roots until the close of the nineteenth century.


Rectal tuberculosis in an HIV-infected patient: case report.
The gastrointestinal (GI) tract has been increasingly affected by tuberculosis, especially in immunocompromised patients. Although strict rectal involvement is rare, the GI site mostly affected is the ileocecal region. Thus, tuberculosis should always be considered in the differential diagnosis of perianal and rectal lesions, and more so in patients infected by the HIV virus. The authors report the case of a 32-year-old man presenting a long-term history of fever, night sweats, weight loss, bloody diarrhea, fecal incontinence, tenesmus, and rectal pain. HIV serology was positive. The patient underwent anoscopy and biopsy, which disclosed the diagnosis of rectal tuberculosis. Thus the patient was referred to an outpatient clinic to follow the standard treatment.


Mid latency and slow vertex responses during pregnancy.
Central auditory pathways picked up electro-physiologically as mid latency responses (MLRs) and slow vertex responses (SVRs) have been studied least in women during their critical periods of life although auditory brainstem responses (ABRs) have been studied by many researchers. In the present study MLRs and SVRs were recorded in 20 pregnant women of age group 18-28 years. Their period of gestation ranged between 26-40 weeks and pregnancy had been uneventful and normal. MLRs and SVRs were recorded from Cz-A1 and Cz-A2 positions with alternating 90 dB sound pressure click stimuli delivered at 5 Hz and 0.5 Hz respectively. 256 stimuli for mid-latency and 64 stimuli for slow vertex responses were averaged and analyzed. Different waves of these auditory evoked responses were compared with 20 age matched non-pregnant females. The data obtained was analyzed for each variable by using unpaired student's T test. Present study did not reveal any difference in MLR waves during pregnancy when compared with the non-pregnant females whereas all the SVR waves were found to be significantly delayed in pregnant females. As SVR generators are found in different cortical areas, it can be said that auditory information processing at the higher centers is slow during pregnancy which in turn could be due to elevated levels of sex hormones specially estrogen and progesterone during pregnancy.


[Total immunization of children against influenza decreases morbidity in a number of diseases among elderly persons during influenza epidemic].
Immunization of children aged 3-6 years in kindergartens and school children aged 7-17 years against influenza with inactivated influenza vaccine was carried out in two districts of the Moscow region. The comparison of morbidity in influenza-like diseases among the immunized children with that among nonimmunized children in control districts revealed that the effectiveness of immunization was 60.9% in kindergartens and 68.8% in schools. The analysis of morbidity in a number of diseases among 158,451 elderly persons not immunized against influenza demonstrated that, in comparison with the control districts, in those districts where mass immunization of children was carried out morbidity in influenza-like diseases among elderly persons was 3.4 times lower and, out of other 10 diseases under study, morbidity in 8 diseases was 1.5-2.6 times lower. As indicated by the data obtained in this study, total anti-influenza immunization of children in organized groups not only essentially decreased influenza morbidity among children, but also greatly decreased morbidity in influenza and a number of diseases, appearing as complications of influenza infection, among nonimmunized elderly persons during influenza epidemic.


Bayesian adaptive estimation of the contrast sensitivity function: the quick CSF method.
The contrast sensitivity function (CSF) predicts functional vision better than acuity, but long testing times prevent its psychophysical assessment in clinical and practical applications. This study presents the quick CSF (qCSF) method, a Bayesian adaptive procedure that applies a strategy developed to estimate multiple parameters of the psychometric function (A. B. Cobo-Lewis, 1996; L. L. Kontsevich & C. W. Tyler, 1999). Before each trial, a one-step-ahead search finds the grating stimulus (defined by frequency and contrast) that maximizes the expected information gain (J. V. Kujala & T. J. Lukka, 2006; L. A. Lesmes et al., 2006), about four CSF parameters. By directly estimating CSF parameters, data collected at one spatial frequency improves sensitivity estimates across all frequencies. A psychophysical study validated that CSFs obtained with 100 qCSF trials ( approximately 10 min) exhibited good precision across spatial frequencies (SD < 2-3 dB) and excellent agreement with CSFs obtained independently (mean RMSE = 0.86 dB). To estimate the broad sensitivity metric provided by the area under the log CSF (AULCSF), only 25 trials were needed to achieve a coefficient of variation of 15-20%. The current study demonstrates the method's value for basic and clinical investigations. Further studies, applying the qCSF to measure wider ranges of normal and abnormal vision, will determine how its efficiency translates to clinical assessment.


Hormone therapy and breast cancer risk.
Hormone therapy (HT) is the most efficacious intervention for the relief of climacteric symptoms. Controversies surrounding HT have left many women puzzled and afraid. Gynecologists are faced with long-standing beneficial assumptions challenged by an abundance of robust detrimental new data, with little guidance on how to interpret these findings. Prescriptions for HT (and incidence of breast cancers in some areas) have fallen over the last 3 years due to anxiety provoked about breast cancer risk and recurrence. The current 'clinical climate' is against HT. Due to a lack of effective alternatives, women suffering from estrogen-deficiency symptoms are still requesting objective information about HT, particularly those at higher risk of breast cancer or those with a past history of breast cancer. In this situation, discussion of the current clinical uncertainty surrounding the use of HT must be undertaken to ensure that women are adequately informed. The objective of this presentation is to provide a framework for understanding breast cancer risk associated with HT. What are the precise molecular mechanisms of estrogen and progestin in the initiation of breast cancer? Does the risk of estrogen-only therapy on breast cancer vary by dose, constituent, route and duration of administration and cessation of use? Does HT, in addition to increasing risk for breast cancer, affect the type of breast cancer (lobular and ductal) diagnosed? Is HT associated with breast cancers that have better prognostic factors? How relevant are the changes in mammographic breast density associated with HT for the evaluation of breast cancer risk? What is the additional global health risk/benefit ratio associated with the selective use of progesterone or progestin that may confer a significant cardiovascular benefit, such as drospirenone? It is currently assumed and tested that new hormones with particular pharmacological profiles may ultimately achieve their therapeutic goal of relieving climacteric symptoms without an associated moderate increased risk of breast cancer.


Hearing sensitivity and measurements of middle ear and eustachian tube function after maxillary osteotomy with advancement surgery.
The nature of audiologic changes after maxillary osteotomy with advancement surgery has not been fully documented. The purpose of this investigation was to better understand the potential alteration of eustachian tube, middle ear pressure and static compliance, and hearing sensitivity in individuals undergoing this type of surgical procedure. Pure tone audiometry and evaluation of middle ear and eustachian tube function were done on seven patients preoperatively and at the 3rd, 6th, and 12th postoperative weeks. Results indicated that, although hearing sensitivity and middle ear and eustachian tube function change from the normal preoperative state during the early postoperative recovery period, they return to normal limits by the 12th postoperative week. These changes suggest the importance of carefully audiologic status in patients undergoing this type of procedure.


Chondrosarcoma of the parapharyngeal space. A case report.
Chondrosarcomas are the malignant cartilagenous tumors and they are seen rarely in the head and neck area. They are usually slow growing lesions. The head and neck chondrosarcomas may show an aggressive course and the occurrence of this malignant cartilagenous tumor in the parapharyngeal space is only a few. They are mostly located in relation with jaw bones and base of the skull. Chondrosarcomas of the parapharyngeal space are limited in number and among them there is no low-grade one. In this case report, a case of low-grade chondrosarcoma which was treated with a simple excision without neck dissection was reported.


Pharmacokinetics of metronidazole in patients undergoing continuous ambulatory peritoneal dialysis.
The pharmacokinetics of metronidazole, its biologically active alcohol metabolite, and its inactive acid metabolite were studied in five noninfected patients undergoing continuous ambulatory peritoneal dialysis and five patients undergoing hemodialysis. The latter were studied on off-dialysis days as a control group. Peritoneal dialysis caused insignificant changes in the apparent volume of distribution, elimination half-life, and total body clearance of metronidazole. Peritoneal dialysis clearance (4.49 +/- 0.88 ml/kg per h [mean +/- standard deviation]) accounted for only 8.9% of total body clearance (50.17 +/- 18.64 ml/kg per h). Analysis of the 24-h area under the serum concentration versus time curves and peritoneal dialysis clearance data for the two metabolites suggested a similar insignificant effect of peritoneal dialysis on their elimination. Metronidazole dialysate concentrations in the first 6-h exchange ranged from 7.6 to 11.7 micrograms/ml. This would suggest that cumulative penetration of metronidazole from the systemic circulation into the peritoneal cavity with dosing every 8 h should lead to adequate concentrations for the treatment of anaerobic peritonitis. For the treatment of systemic anaerobic infections, it would appear at present that metronidazole dosage adjustments are not necessary in patients undergoing continuous ambulatory peritoneal dialysis. The potential for metabolite accumulation was noted in this study. If further studies confirm that excessive serum metabolite concentrations are toxic, dosage reduction in this group of patients may be warranted.


[Hepatitis-B-associated vasculitis. Clinical course with glucocorticoid and alpha-interferon therapy].
A 31-year-old women with chronic active hepatitis B (HBs antigen-positive, HBe antigen-negative) developed a painful petechia rash on both lower legs and the inner surface of the thighs. Histology of a skin biopsy revealed leucocytoclastic vasculitis. The affected skin areas contained HBs antigen and immunoglobulins. Immunosuppressive treatment with initially 60mg/d prednisolone improved the skin condition but activated the chronic hepatitis, GPT rising up to 240 U/l. The steroid treatment had to be discontinued. Subsequently the transaminases became normal but the vasculitis foci recurred. The patient was therefore given alpha-interferon, three times 5 mill. IU weekly subcutaneously for 6 months. The skin lesions disappeared and the circulating HBV-DNA decreased. But the HBs antigen could not be eliminated. It is to be noted that 12 months after the end of the alpha-interferon treatment the vasculitis has not recurred. - This case and published reports indicate that interferon treatment is effective against HBV-associated and immunoglobulin-complex mediated disease.


SSRIs and the syndrome of inappropriate antidiuretic hormone secretion.
Selective serotonin reuptake inhibitors, which include some of the mostly widely prescribed drugs in the United States, produce fewer adverse effects than other types of antidepressants. But their use can be associated with disruption of the action of antidiuretic hormone in the body, which wreaks havoc with homeostasis. This may lead to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is characterized by hyponatremia, a potentially fatal condition that is typically asymptomatic until it becomes severe. SIADH is more likely in some populations, including people who are elderly or who take diuretics. Serum sodium levels should be monitored closely in those at higher risk.


Metabolic syndrome does not improve the prediction of 5-year cardiovascular disease and total mortality over standard risk markers. Prospective population based study.
Metabolic syndrome (MS) is widely believed to be an important risk factor for cardiovascular disease (CVD). We assessed whether a model based on MS improved prediction of CVD and total mortality over the Framingham's general CVD system (FRS) and whether MS was better than its individual components. Prospective cohort study of 855 participants randomly selected from the general population. Cox proportional hazards models were used to estimate the hazard ratios selecting a composite endpoint of CVD and total mortality. The performance of the FRS was compared with that of 4 MS-based models that differed in their use of individual components of MS as well as in the use of optimized cut-points of MS. The assessment included metrics of discrimination, calibration, and risk reclassification. Of all the models, only the model containing the 5 optimized components of MS improved model fit (deviance 10.7, P = 0.005), discrimination (difference of areas under the receiving operating curves 0.018), and risk reclassification in participants without events (net reclassification index 5.97, P = 0.01). The addition of optimized waist circumference to the FRS model improved the performance more than any other MS-based model. Every model containing the dichotomous definition of MS failed to improve model fit, discrimination, and risk reclassification. MS did not contribute predictive information over the FRS for the 5-year risk of CVD and total mortality. Some individual components of MS, in particular waist circumference, might play a role as part of the FRS provided their cut-off points are optimized.


Ureterovaginal fistula following laparoscopic assisted vaginal hysterectomy: case report.
Ureterovaginal fistula following laparoscopic assisted vaginal hysterectomy is reported. The injury was missed in the immediate post-operative period. There was delay in urological consultation. The patient later developed a ureterovaginal fistula which was repaired successfully with a ureteroneocystostomy four months later after the patient was seen in several hospitals. This case is reported to highlight one of the serious complications of laparoscopic surgery that can go unnoticed. The causes of ureteral injuries in laparoscopic surgery, prevention and management protocols are discussed.


Hyperphosphorylated Tau Relates to Improved Cognitive Performance and Reduced Hippocampal Excitability in the Young rTg4510 Mouse Model of Tauopathy.
Tau hyperphosphorylation at several sites, including those close to its microtubule domain (MD), is considered a key pathogenic event in the development of tauopathies. Nevertheless, we recently demonstrated that at the very early disease stage, tau phosphorylation (pTau) at MD sites promotes neuroprotection by preventing seizure-like activity. To further support the notion that very early pTau is not detrimental, the present work evaluated the young rTg4510 mouse model of tauopathy as a case study. Thus, in mice at one month of age (PN30-35), we studied the increase of pTau within the hippocampal area as well as hippocampal and locomotor function. We used immunohistochemistry, T-maze, nesting test, novel object recognition test, open field arena, and electrophysiology. Our results showed that the very young rTg4510 mouse model has no detectable changes in hippocampal dependent tasks, such as spontaneous alternation and nesting, or in locomotor activity. However, at this very early stage the hippocampal neurons from PN30-35 rTg4510 mice accumulate pTau protein and exhibit changes in hippocampal oscillatory activity. Moreover, we found a significant reduction in the somatic area of pTau positive pyramidal and granule neurons in the young rTg4510 mice. Despite this, improved memory and increased number of dendrites per cell in granule neurons was found. Altogether, this study provides new insights into the early pathogenesis of tauopathies and provides further evidence that pTau remodels hippocampal function and morphology.


Functional analysis of the long-range regulatory element of BMP2 gene.
Recently, several pedigree-based studies have shown that abnormal replication of an enhancer element regulatory region in the downstream of the bone morphogenetic protein 2 (BMP2) gene is the cause of brachydactyly type A2 (BDA2). However, the exact molecular function of this regulatory region is unclear, and even conflicting results have emerged. In this study, based on bioinformatics analysis, we amplified target fragments of different lengths in this regulatory region by PCR technology, including a highly conserved 2.1 kb core sequence and 3 fragments that can completely cover the core 2.1 kb fragment. Then, the gene recombination vectors were constructed, and the biological function of these fragments was analyzed by the dual-luciferase reporter gene technology system. We found that the highly conserved 2.1 kb fragment did not have enhancer activity, while all of three truncated fragments showed strong enhancer activity. The results suggest that the expression regulation mode of the BMP2 gene is very complex. For the downstream regulatory region, selecting fragments of different lengths may have different effects on the regulation of BMP2 expression, which may due to the fragments with different lengths carrying different regulatory elements in the number of types. In summary, this study revealed the complexity of BMP2 gene regulatory elements, and provided new clues and directions for the subsequent in-depth exploration of the molecular pathogenic mechanism of BDA2.


A distributed spatio-temporal EEG/MEG inverse solver.
We propose a novel l(1)l(2)-norm inverse solver for estimating the sources of EEG/MEG signals. Based on the standard l(1)-norm inverse solvers, this sparse distributed inverse solver integrates the l(1)-norm spatial model with a temporal model of the source signals in order to avoid unstable activation patterns and "spiky" reconstructed signals often produced by the currently used sparse solvers. The joint spatio-temporal model leads to a cost function with an l(1)l(2)-norm regularizer whose minimization can be reduced to a convex second-order cone programming (SOCP) problem and efficiently solved using the interior-point method. The efficient computation of the SOCP problem allows us to implement permutation tests for estimating statistical significance of the inverse solution. Validation with simulated and human MEG data shows that the proposed solver yields source time course estimates qualitatively similar to those obtained through dipole fitting, but without the need to specify the number of dipole sources in advance. Furthermore, the l(1)l(2)-norm solver achieves fewer false positives and a better representation of the source locations than the conventional l(2) minimum-norm estimates.


Ultrastructural observations on morphogenesis of atypical cilia.
Though ultrastructural studies of bronchial epithelium both in man and in experimental animals revealed in a variety of conditions the presence of pathologically altered cilia, little is known about their genesis and significance. In this work we have described the alterations noticed in ciliary morphology during the formation of atypical cilia. A probable mechanism for their production is also proposed on the basis of our results.


The serum level of endothelin in patients with hand-arm vibration syndrome.
The authors discuss the relationship of serum concentrations of endothelin in patients with vascular disease due to vibration and the severity of the disease; the highest concentrations were found in the most advanced forms of disease. Combination of the vascular disease due to vibration with complicating cardiovascular diseases is also discussed. The authors prepared methodical norms for the elaboration and evaluation of the results of serum concentrations of endothelin. These norms are useful for comparing studies in various regions and for international cooperation. The paper presents preliminary results so far of small group of patients. The examination could be a useful additional method for the classification and assessment of severity and prognosis of the disease.


1,3,5-2,4,6-functionalized, facially segregated benzenes-exploitation of sterically predisposed systems in supramolecular chemistry.
In the present article, we introduce the unique steric features of 1,3,5-substituted triethylbenzenes as a design principle for host molecules and supramolecular systems. Due to steric gearing, all three functional substituents are disposed on the same side of the phenyl plane. The use of this benzene scaffold has lead to the synthesis of various receptor molecules for a wide range of different guest species. Furthermore, the facially segregated systems can be used as building blocks with a controlled conformation in the synthesis of macrocycles or self-assembled supramolecular systems.


[Tumors of the nasal cavity in human immunodeficiency virus infection. A case of polyclonal lymphoid hyperplasia].
HIV virus infection is frequently accompanied by polyclonal or monoclonal lymphoid proliferations. The authors report the first case of a tumour of the cavum in a Haitian subject with HIV infection. This large tumour was associated with parotid swelling and a buccal and ocular sicca syndrome. Histological examination revealed Sjögren type of lympho-epithelial infiltration in the parotid and salivary glands. Biopsy of the cavum demonstrated lymphoid hyperplasia without a monoclonal component. There was no lymphoid proliferation outside of the ear, nose and throat region. The various benign and malignant lymphoid proliferations observed during HIV infection are recalled. Their pathophysiology is discussed: role of EBV in B cell lymphoid proliferations, specific cytotoxicity against cells infected by HIV in T8 proliferations.


Combining a GLP-1 receptor agonist and basal insulin: study evidence and practical considerations.
Most patients with diabetes mellitus require multiple medications to achieve glycemic goals. Considering this and the increasing incidence of type 2 diabetes worldwide, the need for effective combination therapy is pressing. Basal insulin and glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes. Though both classes of medication are exclusively injectable, which may cause initial hesitation from providers, evidence for their combined use is substantial. This review summarizes the theoretical benefit, supporting evidence, and implementation of a combined basal insulin-GLP-1 receptor agonist regimen. Basal insulin added to a GLP-1 receptor agonist reduces hemoglobin A1c (HbA1c) without weight gain or significantly increased hypoglycemia. A GLP-1 receptor agonist added to basal insulin reduces HbA1c and body weight. Compared with the addition of meal-time insulin to basal insulin, a GLP-1 receptor agonist produces similar or greater reduction in HbA1c, weight loss instead of weight gain, and less hypoglycemia. Gastrointestinal adverse events are common with GLP-1 receptor agonists, especially during initiation and titration. However, combination with basal insulin is not expected to augment expected adverse events that come with using a GLP-1 receptor agonist. Basal insulin can be added to a GLP-1 receptor agonist with a slow titration to target goal fasting plasma glucose. In patients starting a GLP-1 receptor agonist, the dose of basal insulin should be decreased by 20 % in patients with an HbA1c ≤8 %. The evidence from 15 randomized prospective studies supports the combined use of a GLP-1 receptor agonist with basal insulin in a broad range of patients with uncontrolled type 2 diabetes.


Spin-Vibronic Mechanism for Intersystem Crossing.
Intersystem crossing (ISC), formally forbidden within nonrelativistic quantum theory, is the mechanism by which a molecule changes its spin state. It plays an important role in the excited state decay dynamics of many molecular systems and not just those containing heavy elements. In the simplest case, ISC is driven by direct spin-orbit coupling between two states of different multiplicities. This coupling is usually assumed to remain unchanged by vibrational motion. It is also often presumed that spin-allowed radiationless transitions, i.e. internal conversion, and the nonadiabatic coupling that drives them, can be considered separately from ISC and spin-orbit coupling owing to the vastly different time scales upon which these processes are assumed to occur. However, these assumptions are too restrictive. Indeed, the strong mixing brought about by the simultaneous presence of nonadiabatic and spin-orbit coupling means that often the spin, electronic, and vibrational dynamics cannot be described independently. Instead of considering a simple ladder of states, as depicted in a Jablonski diagram, one must consider the more complicated spin-vibronic levels. Despite the basic ideas being outlined in the 1960s, it is only with the advent of high-level theory and femtosecond spectroscopy that the importance of the spin-vibronic mechanism for ISC in both fundamental as well as applied research fields has been revealed with significant impact across chemistry, physics, and biology. In this review article, we present the theory and fundamental principles of the spin-vibronic mechanism for ISC. This is followed by empirical rules to estimate the rate of ISC within this regime. The most recent developments in experimental techniques, theoretical methods, and models for the spin-vibronic mechanism are discussed. These concepts are subsequently illustrated with examples, including the ISC mechanisms in transition metal complexes, small organic molecules, and organic chromophores.


Communication: Simplified two-beam rotational CARS signal generation demonstrated in 1D.
We explore a novel phase matching scheme for gas-phase rotational coherent anti-Stokes Raman spectroscopy (CARS). The scheme significantly simplifies the employment of the technique in general. Two laser beams, one broadband and one narrowband, are crossed at arbitrary angle and the generated rotational CARS signal, copropagating with the probe beam, is isolated using a polarization gating technique. The effect of phase-vector mismatch for various experimental implementations was measured experimentally and compared to calculations. The spatial resolution of the current technique is improved by more than an order of magnitude over standard gas-phase CARS experimental arrangements, providing an interaction length of less than 50 μm when desired. Both the pump and Stokes photons originate from the broadband pulse, and are therefore automatically overlapped temporally and spatially. Significantly improved signal levels are achieved because of both the ease of alignment and the higher pulse energy available to the pump and Stokes fields. We demonstrate the technique for single-laser-shot 1D rotational CARS signal generation over approximately a 1 cm field in a flame.


Traditional and novel imaging modalities for advanced prostate cancer: A critical review.
Accurate detection of metastatic prostate cancer in the setting of preoperative staging as well as posttreatment recurrence is crucial to provide patients with appropriate and timely treatment of their disease. This has traditionally been accomplished with a combination of computed tomography, magnetic resonance imaging, and bone scan. Recently, more novel imaging techniques have been developed to help improve the detection of advanced and metastatic prostate cancer. This review discusses the efficacy of the traditional imaging modalities as well as the novel imaging techniques in detecting metastatic prostate cancer. Articles discussed were gathered through a formal PubMed search.


Autonomic modulation, spontaneous baroreflex sensitivity and fatigue in young men after COVID-19.
Impaired autonomic modulation and baroreflex sensitivity (BRS) have been reported during and after COVID-19. Both impairments are associated with negative cardiovascular outcomes. If these impairments were to exist undetected in young men after COVID-19, they could lead to negative cardiovascular outcomes. Fatigue is associated with autonomic dysfunction during and after COVID-19. It is unclear if fatigue can be used as an indicator of impaired autonomic modulation and BRS after COVID-19. This study aims to compare parasympathetic modulation, sympathetic modulation, and BRS between young men who had COVID-19 versus controls and to determine if fatigue is associated with impaired autonomic modulation and BRS. Parasympathetic modulation as the high-frequency power of R-R intervals (lnHFR-R), sympathetic modulation as the low-frequency power of systolic blood pressure variability (LFSBP), and BRS as the -index were measured by power spectral density analysis. These variables were compared between 20 young men who had COVID-19 and 24 controls. Independent t-tests and Mann-Whitney U tests indicated no significant difference between the COVID-19 and the control group in: lnHFR-R, P=0.20; LFSBP, P=0.11, and -index, P=0.20. Fatigue was not associated with impaired autonomic modulation or BRS. There is no difference in autonomic modulations or BRS between young men who had COVID-19 compared to controls. Fatigue did not seem to be associated with impaired autonomic modulation or impaired BRS in young men after COVID-19. Findings suggest that young men might not be at increased cardiovascular risk from COVID-19-related dysautonomia and impaired BRS.


[Multiple meningeal and cerebral involvement revealing multifocal tuberculosis in an immunocompetent patient].
Tuberculosis is a public health problem in Morocco. Central nervous system involvement is nevertheless rare, occurring in the context of multifocal or miliary tuberculosis. However, it may be a mode of revelation even in an immunocompetent subject. We report the case of a 30-year old man with language disorder accompanied by significant impairment of general condition. Clinical examination showed Broca's motor aphasia, right-sided pyramidal syndrome and latero-cervical adenopathies. HIV serologic test was negative. Brain MRI showed lesions associating multiple intracranial tuberculomas and meningoencephalitis. Thoracic CT scan showed multiple pulmonary micronodules, cavity wall thickening and bronchiectasia of the right fowler and culmen. Lymph node biopsy revealed typical architecture of a TB granuloma. The diagnosis of multifocal tuberculosis was retained and the patient received anti-bacillary therapy associated with corticosteroid therapy with good clinico-radiological evolution. This study is peculiar due to the appearance and the seat of tuberculous lesions on brain imaging, the absence of immunodeficiency, a good evolution under treatment. It highlights the role of active and exhaustive assessment of associated extracerebral tuberculous infection in the case of cerebromeningeal lesion suggestive of tuberculosis.