Mohs micrographic surgery: a review of indications, technique, outcomes, and considerations.
Mohs micrographic surgery is a specialized form of skin cancer surgery that has the highest cure rates for several cutaneous malignancies. Certain skin cancers can have small extensions or "roots" that may be missed if an excised tumor is serially cross-sectioned in a "bread-loaf" fashion, commonly performed on excision specimens. The method of Mohs micrographic surgery is unique in that the dermatologist (Mohs surgeon) acts as both surgeon and pathologist, from the preoperative considerations until the reconstruction. Since Dr. Mohs's initial work in the 1930s, the practice of Mohs micrographic surgery has become increasingly widespread among the dermatologic surgery community worldwide and is considered the treatment of choice for many common and uncommon cutaneous neoplasms. Mohs micrographic surgery spares the maximal amount of normal tissue and is a safe procedure with very few complications, most of them managed by Mohs surgeons in their offices. Mohs micrographic surgery is the standard of care for high risks basal cell carcinomas and cutaneous squamous cell carcinoma and is commonly and increasingly used for melanoma and other rare tumors with superior cure rates. This review better familiarizes the dermatologists with the technique, explains the difference between Mohs micrographic surgery and wide local excision, and discusses its main indications.


Caries prevalence and tooth surface distribution in a group of 5-year-old Italian children.
This was to investigate caries experience and patterns in a sample of 5-year-old children attending nursery schools in the Veneto Region (Italy). Cross sectional study. The study was carried out between September 2005 and May 2006 with 348 randomly selected 5-year-old children. Two calibrated dentists using an artificial light, a plane dental mirror and a dental probe performed clinical dental examination. World Health Organisation (WHO) diagnostic criteria for dental caries: dmft, dmfs and SiC indexes were used to measure the severity of the disease. dmfs scores were analysed either as a continuous continuous (calculating means and standard deviations) or as a categorical variable (providing proportions). Pearson's chi square test for comparison between groups and Wilcoxon signed-rank test for distribution of dmfs scores between pairs of contiguous molars were used. The most commonly affected teeth were primary molars, (78% of the overall sample), especially in the mandible. The surfaces of molars most often affected were the occlusal (52%). Proximal surfaces were affected more in first than in second primary molars. Dental caries occurred most often in the maxilla. The frequency of caries in anterior teeth was low (12%). Caries experience in the primary dentition showed a symmetrical distribution localized on primary molars, most often in their occlusal surface. Caries in anterior teeth was uncommon.


Poppy seeds: implications of consumption.
Three white poppy seed samples of Papaver somniferum L were found to contain total morphine (free and bound) in the range 58.4 to 62.2 micrograms/g seeds and total codeine (free and bound) in the range 28.4 to 54.1 micrograms/g seeds. Soaking seeds in water was found to remove 45.6 per cent of the free morphine and 48.4 per cent of the free codeine. In ingesting a curry meal or two containing various amounts of washed seeds (morphine intake: 200.4 to 1002 micrograms; codeine intake: 95.9 to 479.5 micrograms), the urinary morphine levels were found to be in the range 0.12 to 1.27 micrograms/ml urine and urinary codeine levels in the range 0.04 to 0.73 micrograms/ml urine. In any large scale screening for abuse of opiate drugs, the possibility of urinary alkaloids arising from consuming food containing poppy seeds must be considered and, if possible, eliminated.


Unraveling neuronal ceroid lipofuscinosis type 2 (CLN2) disease: A tertiary center experience for determinants of diagnostic delay.
To evaluate the clinical phenotype, disease course, laboratory, and genetic features of patients with CLN2 disease over a 20 year period with a special emphasis on risk factors for diagnostic delay. Thirty patients (23 families) with CLN2 disease, evaluated between 1996 and 2019 in a tertiary referral center in Turkey, were included. Clinical features, diagnostic pathway, disease course, genetic data, electrophysiological, and neuroimaging findings were analyzed, retrospectively. The patients diagnosed between 1996 and 2009, and 2010-2019 were defined as group 1 (G1), and group 2 (G2), respectively. Patients in these two groups were also compared. The median age at symptom-onset was 36 months (20 months-7 years). Most common presenting symptoms were seizures (70%), followed by language delay (43%), and psychomotor regression (27%). Median age at diagnosis was 5.2 years (1.6-11 years) with a median 27 months (1 month-7 years) of diagnostic delay. Age at diagnosis was earlier in G2 (4.6 years vs 7 years, p = 0.002), with a shorter time to diagnosis (21 months vs 39 months, p = 0.004). Median time between the onset of first symptoms and death was 8.3 years (SE 1.0). Electroencephalograms (EEG) revealed abnormal features predominantly in posterior hemispheral regions and a photoparoxysmal response to intermittent photic stimulation was detected in 53% of the patients. Cerebellar (96%)/cerebral atrophy (83%), and white matter changes (57%) were the most common radiological abnormalities. Most of our patients presented with late-infantile onset seizures. Despite increased availability of enzymatic and molecular testing, there is still a considerable diagnostic delay.


Comparative safety and costs of transparent versus gauze wound dressings in intravenous catheterization.
The type of dressing selected for intravascular catheters may influence costs and complications. We carried out a clinical trial to compare the safety and costs of transparent and gauze dressings. We did not find differences in complication rates between transparent (34.1%) and gauze (26.5%) dressings (P = .62). The total cost per patient was $24.82 for transparent and $38.85 for gauze. The results indicate similar safety but increased cost associated with gauze dressings.


Effects of nurse-managed telemonitoring on blood pressure at 12-month follow-up among urban African Americans.
Nearly one in three adults in the United States has hypertension. Hypertension is one of the largest risk factors for cardiovascular diseases, and it is growing in prevalence, especially among African Americans. To test the hypothesis that individuals who participate in usual care (UC) plus blood pressure (BP) telemonitoring (TM) will have a greater reduction in BP from baseline to 12-month follow-up than would individuals who receive UC only. A two-group, experimental, longitudinal design with block stratified randomization for antihypertensive medication use was used. African Americans with hypertension were recruited through free BP screenings offered in the community. Data were collected through a structured interview and brief physical exam. Cross tabs, repeated measures analysis of variance, and independent t tests were used to analyze the study's hypothesis. The TM intervention group had a greater reduction in systolic BP (13.0 mm Hg) than the enhanced UC group (7.5 mm Hg; t = -2.09, p = .04) from baseline to the 12-month follow-up. Although the TM intervention group had a greater reduction in diastolic BP (6.3 mm Hg) compared with the enhanced UC group (4.1 mm Hg), the differences were not statistically significant (t = -1.56, p = .12). : Telemonitoring of BP resulted in clinically and statistically significant reductions in systolic BP over a 12-month period; if maintained over a longer period of time, the reductions could improve care and outcomes significantly for African Americans with hypertension.


Responses of Porcupine and Wntless proteins to oxidative, hypoxic and endoplasmic reticulum stresses.
The WNT (Wingless and Int-1) proteins play a role in stem cell development and cell differentiation. Mutations in the WNT proteins lead to the development of various tumours, including gastric tumours. Porcupine (PORCN) is a palmitoyltransferase and Wntless (WLS) is a dedicated WNT transport protein that modify and fold the WNT proteins respectively and are involved in their proper secretion and binding to the frizzled (FZD) receptor and the lipoprotein receptor-related protein 5 or 6 (LRP5/6). We investigated how modifications of PORCN and WLS result in changes in WNT expression and secretion from cells under stress conditions that occur in the tumour microenvironment (hypoxia, oxidative stress, endoplasmic reticulum (ER) stress). In the present study, we found the mRNA expression of both PORCN and WLS were significantly increased with treatments inducing oxidative stress (antimycin A) and proteasome inhibition (MG-132), in human colon cancer (HCT116) and human intestinal epithelial cell-6 (HIEC-6) cells. Treatment with ER stressors thapsigargin, tunicamycin, and dithiolthreitol significantly increased PORCN gene expression, while treatment with thapsigargin and dithiolthreitol increased WLS gene expression. The expression of PORCN and WLS proteins increased with hypoxia and ER stressor treatments in both HCT116 and HIEC-6 cells. All stressors used in this study increased beta-catenin (β-catenin) expression in HCT116 cells. Our results suggest that these stressors alter PORCN, WLS and β-catenin expression and function which may, in turn, alter WNT secretion. Silencing the expression of PORCN and WLS with siRNA expression reduced the expression of WLS and WNT3A in HCT116 cells. The possibility exists that PORCN specifically may be involved in a novel signaling pathway, independent of its palmitoleation of the WNT proteins and its role in their secretion, that is rate-limiting for cancer cell growth and tumorigenesis, within the tumour microenvironment.


Latissimus dorsi muscle blood flow during synchronized contraction: implications for cardiomyoplasty.
Damage in latissimus dorsi muscle flaps has been reported after clinical and experimental cardiomyoplasty, and an ischemic origin has been suggested. In situ, preconditioned latissimus dorsi muscles in 5 sheep were stimulated in either 1:1 (muscle: heart) or 1:2 synchrony with the systolic phase of the cardiac cycle, using a burst duration of either 21% or 35% of the cycle. Thoracodorsal artery blood flow and thoracodorsal venous lactate concentrations were measured before and immediately after a 3-minute period of stimulation. The exercise-induced augmentation of thoracodorsal artery blood flow was significantly (p < 0.05) less with a 1:2 regimen than a 1:1 regimen, for both a 21% (88%; 95% confidence interval [CI], 55.6% to 127.3% versus 138.9%; CI, 97.6% to 188.8%) and 35% burst duration (123.2%; CI, 84.7% to 169.9% versus 167.0; CI, 120.8% to 222.6%). After cessation of stimulation, reactive hyperaemia was observed in 3 of 5 animals with 1:1 21% burst stimulation, and in 5 of 5 animals with a 35% burst duration, but was not seen after 1:2 regimens. A significant (p < 0.01) increase in thoracodorsal venous lactate levels was present after 1:1 35% burst stimulation (34.9%; CI, 9.9% to 65.6%), but lactate levels tended to fall when a 1:2 ratio was used (15.9%; CI, -3.2% to 31.5%; p < 0.1). One-to-one stimulation regimens may be detrimental to latissimus dorsi blood flow, and an adaptive, rather than fixed, burst duration may be preferable. These findings have important implications for the cardiomyoplasty procedure.


Polytetrafluoroethylene (PTFE) suture vs fiberwire and polypropylene in flexor tendon repair.
In this study, we evaluate the value of novel suture material based on monofilamentous-extruded polyfluoroethylene (PTFE) compared to polypropylene (PPL) and Fiberwire (FW). 60 flexor tendons were harvested from fresh cadaveric upper extremities. 4-0 sutures strands were used in the PPL, FW and PTFE group. Knotting properties and mechanical characteristics of the suture materials were evaluated. A 4-strand locked cruciate (Adelaide) or a 6-strand (M-Tang) suture technique was applied as core sutures for a tendon repair. Two-way ANOVA tests were performed with the Bonferroni correction. Stable knotting was achieved with 5 throws with the PPL material, 7 throws for FW and 9 throws for PTFE. In the PPL group, linear tensile strength was 45.92 ± 12.53 N, in the FW group 80.11 ± 18.34 N and in the PTFE group 76.16 ± 29.10 N. FW and PTFE are significantly stronger than PPL but show no significant difference among each other. Similar results were obtained in the subgroup comparisons for different repair techniques. The Adelaide and the M-Tang knotting technique showed no significant difference. Fiberwire showed superior handling and knotting properties in comparison to PTFE. However, PTFE allows easier approximation of the stumps. In both, M-Tang and Adelaide repairs, PTFE was equal to FW in terms of repair strength. Both PTFE and FW provide for a robust tendon repair so that early active motion regimens for rehabilitation can be applied.


The effect of Total resistance exercise vs. aquatic training on self-reported knee instability, pain, and stiffness in women with knee osteoarthritis: a randomized controlled trial.
Knee Instability (KI) is described as a sense of knee buckling, shifting, or giving way during the weight bearing activities. High prevalence (60-80%) has been reported for KI amongst the patients with knee osteoarthritis (KOA). In this line, the present study targeted the effect of two interventions on self-reported KI and affected factors. In this single blind, randomized, and controlled trial, 36 patients with radiographic grading (Kellgren-Lawrence ≥ II) of KOA were selected. Patients were divided into three groups namely, aquatic (n = 12), Total Resistance exercises (TRX) (n = 12) and control (n = 12) by random. Then both 8-week TRX and aquatic exercises were carried out by experimental groups. The following measure were taken before and after interventions: Pain by visual analog scale (VAS), balance by Berg Balance Scale (BBS), quadriceps strength by dynamometer, knee flexion range of motion (ROM) by inclinometer, knee stiffness with Western Ontario and McMaster Universities Osteoarthritis (WOMAC), and self-reported KI with Felson's questionnaire. The results demonstrated that KI, VAS, BBS improved over time both in TRX and aquatic groups significantly (p < 0.05), but WOMAC(stiffness), knee flexion ROM, and quadriceps strength were significantly improved over time only for TRX (p < 0.05). Post hoc test, also, showed that there were significant differences between interventions and control groups (p < 0.05) for the VAS, KI, BBS, but for WOMAC(stiffness), a significant difference was observed only between TRX and control groups (p = 0.05). Although TRX and aquatic interventions had a similar effect on the patients' balance, pain and KI, TRX had more effect on WOMAC(stiffness), quadriceps strength, and knee flexion ROM than aquatic exercises. This study was registered in the Iranian Clinical Trial Center with the number IRCT20181222042070N1, http://www.irct.ir/trial/36221, registered 02 February 2019.


Vitality surveillance at distance using thin-film tandem-like narrowband near-infrared photodiodes with light-enhanced responsivity.
Remote measurement of vital sign parameters like heartbeat and respiration rate represents a compelling challenge in monitoring an individual's health in a noninvasive way. This could be achieved by large field-of-view, easy-to-integrate unobtrusive sensors, such as large-area thin-film photodiodes. At long distances, however, discriminating weak light signals from background disturbance demands superior near-infrared (NIR) sensitivity and optical noise tolerance. Here, we report an inherently narrowband solution-processed, thin-film photodiode with ultrahigh and controllable NIR responsivity based on a tandem-like perovskite-organic architecture. The device has low dark currents (<10-6 mA cm-2), linear dynamic range >150 dB, and operational stability over time (>8 hours). With a narrowband quantum efficiency that can exceed 200% at 850 nm and intrinsic filtering of other wavelengths to limit optical noise, the device exhibits higher tolerance to background light than optically filtered silicon-based sensors. We demonstrate its potential in remote monitoring by measuring the heart rate and respiration rate from distances up to 130 cm in reflection.


Oligonucleotide primers for polymerase chain reaction amplification of human immunoglobulin variable genes and design of family-specific oligonucleotide probes.
In recent work, the polymerase chain reaction (PCR) has been used to amplify rearranged mouse and human immunoglobulin heavy and kappa light chain variable (V) genes. Here we have optimized the design of the PCR primers for human V genes and used them to amplify cDNA from human peripheral blood lymphocytes. Cloning and sequencing revealed a diverse repertoire of V genes, and the presence of members of each human V gene family. After alignment of the sequences, we identified a region conserved within V gene families, but differing between families, and used this to design family-specific oligonucleotide probes.


Molecular Modelling and Atomistic Insights into the Binding Mechanism of MmpL3 Mtb.
Mycobacterial membrane proteins Large (MmpLs), which belong to the resistance, nodulation, and division (RND) protein superfamily, play critical roles in transporting polymers, lipids, and immunomodulators. MmpLs have become one of the important therapeutic drug targets to emerge in recent times. In this study, two homology modelling techniques, Modeller and SWISS-MODEL, were used in modelling the three-dimensional protein structure of the MmpL3 of Mycobacterium tuberculosis using that of M. smegmatis as template. MmpL3 inhibitors, namely BM212, NITD304, SPIRO, and NITD349, in addition to the co-crystalized ligands AU1235, ICA38, SQ109 and rimonabant, were screened against the modelled structure and the Mmpl3 of M. smegmatis using molecular docking techniques. Protein-ligand interactions were analysed using molecular dynamics simulations and Molecular Mechanics Poisson-Boltzmann surface area computations. Novel residues Gln32, Leu165, Ile414, and Phe35 were identified as critical for binding to M. tuberculosis MmpL3, and conformational dynamics upon inhibitor binding were discussed.


Predicting and Managing Treatment Non-Response in Posttraumatic Stress Disorder.
This review aims to synthesize existing research regarding the definition of treatment resistance in posttraumatic stress disorder (PTSD), predictors of treatment non-response to first-line interventions, and emerging second-line PTSD treatment options into an accessible resource for the practicing clinician. The concept of treatment resistance in PTSD is currently poorly defined and operationalized. There are no well-established predictors of treatment non-response utilized in routine clinical care, but existing research identifies several potential candidate markers, including male gender, low social support, chronic and early life trauma exposure, comorbid psychiatric disorders, severe PTSD symptoms, and poor physical health. The most promising available treatment options for PTSD patients non-responsive to first-line psychotherapies and antidepressants include transcranial magnetic stimulation and ketamine infusion. Methylenedioxymethamphetamine-assisted psychotherapy also appears promising but is only available in a research context. These options require careful consideration of risks and benefits for a particular patient. More research is required to develop a robust, clinically-useful definition of treatment resistance in PTSD; identify reliable, readily assessable, and generalizable predictors of PTSD treatment non-response; and implement measurement and prediction in clinical settings to identify individuals unlikely to respond to first-line treatments and direct them to appropriate second-line treatments.


Formation of osteoclasts and osteoblast-like cells in long-term human bone marrow cultures.
A culture system for human osteoclasts is described. It is based on incubation of mononuclear marrow cells for three weeks in the presence of 1,25 dihydroxyvitamin D3. The resulting cells exhibited all the classic characteristics of osteoclasts. They formed a true syncytium with up to 25 nuclei per cell. The cells revealed a strong positive reaction for tartrate-resistant acid phosphatase and a ruffled border. When these cells were cultured on 100 microns thick human dentine slices for three weeks, typical resorption pits were formed. In the culture, alkaline phosphatase-positive osteoblast-like cells were formed in the vicinity of osteoclasts. This culture system permits studies of human osteoclasts and their interaction with osteoblast cell precursors in the human bone marrow.


Toxicological evaluation of food additives. Toxicological evaluation over estimation of potential high intake to permitted levels of use of food additives and vice versa.
Permitted levels of use for food additives should agree with the acceptable daily intakes (ADIs) established by toxicologists. To ensure accordance, nutritional and physiological factors can be used to estimate high intakes of food and beverages. Appetite and thirst (energy and liquid requirements) are such quantitative factors. They are universal and, if placed on the same level as the ADI, i.e., expressed on a kilogram of body weight basis, can be used to estimate high intakes of an additive. This tool can be easily used to judge whether a suggested level of use may cause consumption of the additive to exceed the ADI. It also tells us to what level (ADI) toxicological clearance should be sought, when the technological need is known. The method is independent of food consumption surveys, but these may be carried out to confirm its forecasts. This paper uses caramel in soft drinks as an example. The approach, also called "the budget method," has been tried out in Denmark and Sweden. It is now being offered as a solution to the problem facing the European Communities: to establish before 1993 a common list of food additives containing quantitative limitations for use.


Low concentrations of methamidophos do not alter AChE activity but modulate neurotransmitters uptake in hippocampus and striatum in vitro.
Methamidophos (Meth) is a toxic organophosphorus compound (OP) that inhibits acetylcholinesterase enzyme (AChE) and induces neurotoxicity. As the mechanism of its neurotoxic effects is not well understood, the aim of the present study was to evaluate the effects of Meth on glutamate and gamma aminobutyric acid (GABA) uptake and correlate with cell viability and AChE and Na(+)/K(+)-ATPase enzyme activities in striatum and hippocampus slices exposed to low concentrations (0.05 to 1.0 μM) of Meth. Hippocampal and striatal slices of rat brain were exposed to Meth for 5 min ([(3)H]Glutamate uptake) or 15 min ([(3)H]GABA uptake) for assays. The enzyme activities and cell viability were also accessed at both times in hippocampal and striatal slices and homogenates. At concentrations that did not inhibit AChE, Meth caused changes in glutamate uptake in striatal (0.05 and 1.0 μM Meth) and hippocampal (1.0 μM Meth) slices. GABA uptake was increased by the pesticide in striatum at 0.5 and 1.0 μM and in hippocampus at 0.05 μM. After 3.5h of Meth exposure, striatal and hippocampal cells showed no changes in viability as well as no inhibition of Na(+)/K(+)-ATPase were observed after 5 or 15 min exposure to Meth in the same brain structures. Results suggest that Meth, even without changing the AChE activity can modify somehow the neurotransmitters uptake. However, further studies are necessary to clarify if this modulation in glutamate or GABA uptake may be responsible to cause some disturbance in behavior or in other neurochemical parameters following low Meth exposure in vivo.


Overexpression of a plant U-box gene TaPUB4 confers drought stress tolerance in Arabidopsis thaliana.
Drought stress frequently results in significant reductions in crop production and yield. Plant U-box proteins (PUB) play a key role in the response to abiotic stress. Despite extensive characterization of PUB in model plants, their roles in wheat abiotic stress response remains unknown. In this study, we identified the physiological function of TaPUB4, a gene encoding the U-box and nuclear localization domains. The transcription level of TaPUB4 was induced by drought (mannitol) and abscisic acid. TaPUB4 displays E3 ubiquitin ligase activity and is located in the nucleus. Overexpression of TaPUB4 in Arabidopsis plants enhanced sensitivity with under ABA condition during early seedling developmental stages. In addition, the stomatal conductance of TaPUB4 was closer to that of WT under ABA conditions. Moreover, TaPUB4 facilitated stomatal response to elevated CO2 emission rates under ABA conditions. TaPUB4-overexpressing Arabidopsis, on the other hand, was more resistant to drought stress in plant development, demonstrating that TaPUB4 positively regulates drought-mediated control of plant growth. Moreover, the ectopic expression of the TaPUB4 gene was significant influential in drought sensitive metrics including survival rate, chlorophyll content, water loss, proline content and the expression of drought stress-response genes. Collectively, our results demonstrate that TaPUB4 may regulate drought stress response and ABA conditions.


A new inexpensive ultrasound-guided central venous catheterization simulation model.
Central venous catheters (CVCs) are life-saving tools for fluid therapy during surgery. Ultrasound-guided CVC placement has been shown to be safe and highly efficient. However, it is difficult for medical workers with less experience in ultrasonography to acquire the necessary skill in a short time. Simulation-based training is a good way to enhance the skill of a beginner. Therefore, in this study, we introduced a new, inexpensive and easily implemented model for ultrasound-guided CVC placement training and assessed the feasibility of this model. This was a quasi-experimental study. Thirty-three anaesthesiology postgraduate year 2 and 3 residents with strong CVC interest were included in a simulator-based training workshop in a department of anaesthesiology. The simulation model consisted of a piece of pork and two latex catheters filled with red and blue ink. The workshop comprised 3 parts: a 10-min introductory lecture, a 15-min orientation on performing ultrasound-guided CVC insertion based on the model, and a 30-min practice session. Participants completed relevant questionnaires before and after the training. Moreover, an examination was held to evaluate their skill with the novel model. All participants indicated that the novel model increased their self-perceived confidence in ultrasound-guided catheterization. They also all reported that the model was adequate for training anaesthesiology residents in ultrasound-guided catheterization. A few individuals thought the model did not mimic the progress of CVC insertion (3 of 33). After training, participants did not show a significant difference in the acquisition of central venous catheterization theory. However, their competency with ultrasound-guided CVC placement was enhanced. This was demonstrated not only based on subjective answers to the following questions, namely, "how do you perform central venous catheterization with ultrasound guidance?" (p < 0.001), "can you perform ultrasound-guided central venous catheterization?" (p < 0.001), and "how much self-confidence do you have in performing ultrasound-guided central venous catheterization?" (p < 0.001), but also in objective performance (evaluation of the core step in ultrasound-guided placement (p < 0.001)). The new simulator is a feasible, inexpensive and easily reproducible tool for training anaesthesiologists in ultrasound-guided central venous catheterization. After the simulation-based training workshop, the competency of residents in performing central venous catheterization with ultrasound guidance improved.


Peripheral quantitative computed tomography of the lower leg in children and adolescents: bone densities, cross-sectional sizes and muscle distribution reference data.
Peripheral quantitative computed tomography is utilised in increasing numbers of paediatric studies, however, very little is known about the reference limits for pQCT tibia measurements. The purpose of this study was to establish country-specific reference data for bone densities, cross-sectional sizes, strength and regional muscle distribution measured by pQCT in children and adolescents. Stratec XCT 2000L apparatus was used. The measurement sites were 4%, 14%, 38% and 66% of the tibia length. The study group consisted of 222 participants (103 girls) aged 4,3-19,4 yrs. ANCOVA was used to assess the main determinants of pQCT outcomes. The LMS method was used to fit the percentile curves for each outcomes. Weight and age were the main determinants for most of the pQCT outcomes. Smoothed percentile curves were developed by age and by height for both sexes. In this study we present reference data for bone densities, cross-sectional size and strength as well as for regional muscle distribution measured by pQCT at certain sites of the lower leg to allow simple calculation of reliable Z scores.


Development of a Pt-graphene nanocomposite-based solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry for the determination of carbamate pesticides in fish.
In the present work, a potential solid-phase extraction (SPE) material based on graphene anchored with platinum nanoparticles (Pt-Graphene) was prepared and characterized by scanning electron micrographs and transmission electron micrograph. The carbamates residues in fish were enriched by SPE filled with Pt-Graphene and detected by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The proposed extraction protocol exhibited satisfactory recoveries (76.5-115.6%), low limit of quantitation values in μg kg-1 level, and good precision for the studied ten carbamates. These results demonstrated the feasibility of the proposed protocol. The developed Pt-Graphene nanoparticles showed excellent performance for extracting analytes at trace levels, indicating that it could be used as a potential SPE sorbent in food residue analysis.


Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in female Syrian hamsters and retains partial susceptibility to treatment.
The SARS-CoV-2 main protease (3CLpro) is one of the promising therapeutic targets for the treatment of COVID-19. Nirmatrelvir is the first 3CLpro inhibitor authorized for treatment of COVID-19 patients at high risk of hospitalization. We recently reported on the in vitro selection of SARS-CoV-2 3CLpro resistant virus (L50F-E166A-L167F; 3CLprores) that is cross-resistant with nirmatrelvir and other 3CLpro inhibitors. Here, we demonstrate that the 3CLprores virus replicates efficiently in the lungs of intranasally infected female Syrian hamsters and causes lung pathology comparable to that caused by the WT virus. Moreover, hamsters infected with 3CLprores virus transmit the virus efficiently to co-housed non-infected contact hamsters. Importantly, at a dose of 200 mg/kg (BID) of nirmatrelvir, the compound was still able to reduce the lung infectious virus titers of 3CLprores-infected hamsters by 1.4 log10 with a modest improvement in the lung histopathology as compared to the vehicle control. Fortunately, resistance to Nirmatrelvir does not readily develop in clinical setting. Yet, as we demonstrate, in case drug-resistant viruses emerge, they may spread easily which may thus impact therapeutic options. Therefore, the use of 3CLpro inhibitors in combination with other drugs may be considered, especially in immunodeficient patients, to avoid the development of drug-resistant viruses.


Temperature dependence of kinetic parameters for hyperthermophilic glutamate dehydrogenase from Aeropyrum pernix K1.
The temperature dependence of the steady-state kinetic parameters for a glutamate dehydrogenase from Aeropyrum pernix K1 was investigated. The enzyme showed a biphasic kinetic characteristic for L-glutamate and a monophasic one for NADP at 50-90 degrees C. At low concentrations of L-glutamate the Km decreased from 2.02 to 0.56 mM and the catalytic efficiency (Vmax/Km) markedly increased (4-150 micromol x mg(-1) x mM(-1)) along with the increase of temperature from 50 to 90 degrees C. At high concentrations of the substrate the Km was fairly high and approximately constant (around 225 mM), and the catalytic efficiency was low and its temperature-dependent change was small. The Km (0.039 mM) for NADP did not change with the increase of temperature. In the reductive amination, the Kms for 2-oxoglutarate (1.81 and 9.37 mM at low and high levels of ammonia, respectively) were independent on temperature, but the Kms for ammonia and NADPH rose from 86 to 185 mM and 0.050 to 0.175 mM, respectively.


Tuber Brain Proportion Determines Epilepsy Onset in Children With Tuberous Sclerosis Complex.
Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder characterized by epilepsy and structural abnormalities of the brain. Little research has been done to explore the relationship between the tuber brain proportion (TBP) and epilepsy. We investigated several quantitative cerebral lesions including TBP on magnetic resonance imaging (MRI) and their impact on the onset age, seizure mode, and antiseizure treatment effectiveness of epilepsy in children with TSC. We reviewed the clinical characteristics and MRI information of 44 children with TSC who had experienced epileptic seizures. Supratentorial tubers were quantitatively manually measured to calculate the TBP. The numbers of cortical/subcortical cyst-like tubers, diffuse lesions, subependymal nodules, and subependymal giant cell astrocytomas were also evaluated. Twelve children (27.3%) had experienced infantile spasms, thirteen children (29.5%) had early-onset epilepsy, and twenty-seven patients (64.3%) had a significant reduction in the frequency of seizures after antiseizure treatments. The median TBP was 9.2%, and diffuse lesions (range: 0-2) and cortical cyst-like lesions (range: 0-17) were seen in seven and seventeen children, respectively. The values of TBP (P < 0.001), diffuse lesions (P < 0.001), and cortical cyst-like tubers (P < 0.001) were all associated with early-onset epilepsy. The values of TBP (P = 0.004) and cortical cyst-like tuber (P < 0.001) were associated with the occurrence of infantile spasms. The values of TBP (P = 0.01), diffuse lesions (P = 0.04), and cortical cyst-like tubers (P = 0.004) were negatively associated with the effectiveness of antiseizure treatments. There was no significant correlation between subcortical cyst-like tuber, subependymal nodule, subependymal giant cell astrocytoma, and epilepsy severity. Increasing abnormality of the cerebral hemispheres, as shown by quantitative MRI analysis including TBP, cortical cyst-like tubers, and diffuse lesions, is associated with measures of more severe epilepsy due to TSC. The values of TBP demonstrate strong significance for early-onset epilepsy.


Microplastics change the leaching of nitrogen and potassium in Mollisols.
Nowadays, the dynamics of nutrients leaching from the soils and their driving mechanism have been focused on, however, it is still unclear how microplastics (MPs) influence the nutrients' leaching in soils. In this study, five concentrations (w/w, 0.0 %, 0.5 %, 1 %, 2 %, 3 %) and three sizes of MPs of polyethylene (PE) (0.15-0.36 mm, 0.36-0.60 mm and 0.60-1.00 mm) influencing the leaching of NO3--N and water-soluble potassium (WSK) was simulated by a column method in Mollisols, and both the pre-fertilization and post-fertilization were considered. The results showed that, before KNO3 addition, there was a negative power function relationship between the NO3--N concentration and the leaching solution volume/leaching time. The amount and concentration of NO3--N leaching was higher in the early leaching stage. Compared with the CK, PE0.5% significantly reduced the leaching amount of WSK, while increased the leaching amount of NO3--N but not significantly. The leaching amount of WSK decreased with the increasing size of PEMP when the PEMP concentration was the same, while NO3--N was opposite. PE0.60-1.00 increased the leaching amount of NO3--N, while reduced the leaching amount of WSK. After KNO3 addition, compared with CK, PE1% significantly reduced the leaching amount of NO3--N, and PE1% had the lowest leaching amount of WSK. However, when the PEMP concentration in the soil reached a certain threshold (w/w, >1 %), the leaching amount of NO3--N and WSK increased gradually with PEMP increasing. PE0.60-1.00 reduced the leaching amount of NO3--N and WSK most obviously. In general, low concentrations (w/w, <1 %) and large sizes (0.60-1.00 mm) of PEMP promoted NO3--N leaching and inhibited the WSK leaching from the soil before the addition of KNO3, however, they both inhibited the leaching of NO3--N and WSK from the soil after addition of KNO3.


Philosophical implications of the systemic and patient-oriented management of chronic heart failure.
Chronic heart failure is a lifelong disease that involves a large variety of symptoms and, ultimately, the entire organism relatively early in the disease process. At least in part, this is in contrast to other chronic conditions such as diabetes, renal failure or cancer. Modern treatment of patients with chronic heart failure goes beyond the mere prescription of vasodilators or inotropes. The multitude of multi-organ involvements and associated symptoms unrelated to pure cardiac contractile failure, as well as the psychosocial burden for patients and their direct environment, calls for a re-engagement with the philosophical aspects of medical care. Such a process may well challenge the approach commonly taken by health care providers. We further suggest a broader and more holistic view of medical care--in this case in regard to heart failure--and one that is based on patients' and physicians' understanding of health and disease, autonomy, suffering, existential values and expectations that might positively affect treatment strategies and outcomes.


Validity and reliability of the Amharic version of supportive care needs survey - short form 34 among cancer patients in Ethiopia.
Supportive care needs survey short form has a total of 34 items that have 5 domains that measure the unmet needs of cancer patients. It is important to validate this tool since there are differences in culture, geographic areas, and clinical care service which influence patients' needs. Therefore, this study aimed to assess the construct validity and reliability of the tool. The study was conducted among 170 cancer patients from April 1st to 30th 2019 in Hawassa hospital, South Ethiopia. Confirmatory factor analysis was done using fit indices. Convergent and discriminant validity was evaluated using average variance extracted and maximum shared variance respectively. Known group validity was checked using the Mann-Whitney U test. The reliability of the instrument was examined using Cronbach's alpha. Domains except for health system and information, and patient care and support maintained convergent and divergent validity. The remaining validity was maintained after removing items that were redundant and double loading. The average variance extracted of domains varied from 0.52-0.81. The Square of correlation between constructs was lower than the average variance extracted for the constructs. The tool had reliability r = 0.932. The root mean square error of approximation was 0.057, comparative fit index 0.954, and the other fit indices were also indicating a good fit. Known groups difference was seen by age and type of treatment taken across the different domains. After the health system and information, and patient care, and support domain validity issues were corrected by removing 8 items, the reduced tool was found to be a valid and reliable tool. The validated tool will be valuable if included in routine cancer care in our clinical settings.


Community-based smoking cessation treatment for adults with high anxiety sensitivity: a randomized clinical trial.
People with anxiety disorders are more likely to smoke and less likely to succeed when they try to quit. Anxiety sensitivity may underlie both phenomena, such that people with high anxiety sensitivity react to interoceptive distress by avoidance. This study aimed to test the efficacy of an exercise program that induced interoceptive distress and thereby created tolerance to this distress in a safe environment. Randomized clinical trial at four YMCA branches in Austin, Texas, USA. Participants [n = 150; 130 (86.7%) white; 101 (67.3%) female; meanage = 38.6, standard deviation (SD)age = 10.4] were adult, daily smokers with high anxiety sensitivity motivated to quit smoking, who reported no regular moderate-intensity exercise. Participants were assigned a YMCA personal trainer who guided them through a 15-week intervention aerobic exercise program. Participants assigned to the personalized intervention trained at 60-85% of their heart rate reserve (HRR), whereas participants assigned to the control intervention trained at 20-40% of their HRR. Participants in both groups received standard behavioral support and nicotine replacement therapy. The primary outcome was biologically verified 7-day point prevalence abstinence (PPA) at 6-month follow-up. Sixty-one per cent of participants were available at the 6-month follow-up. PPA at 6 months was higher in the personalized intervention than the control intervention [27.6 versus 14.8%; odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.28, 3.80, P = 0.005], assuming missing at random. Anxiety sensitivity declined in both groups with no evidence that this differed between groups. An exercise program of high intensity increased abstinence from smoking in people with high anxiety sensitivity, but may not have done so by reducing anxiety sensitivity.


New fecal occult blood tests may improve adherence and mortality rates.
Several new fecal occult blood tests have advantages over older ones when used for colorectal cancer screening. Fecal immunochemical tests can detect antibodies to human globin in the stool and can be used without the dietary restrictions needed with traditional guaiac tests. Although colonoscopy is often considered the gold standard, we hope that these new tests will allow more people to be screened and more cases of colorectal cancer to be detected early.


Nucleotide sequence for cDNA of bovine mitochondrial ATP-dependent protease and determination of N-terminus of the mature enzyme from the adrenal cortex.
We have determined the cDNA sequence encoding bovine mitochondrial ATP-dependent Lon protease. Since the 5'-end region of the cDNA was highly GC-rich and thus could not be amplified by the 5'-RACE method, a genomic DNA fragment containing an in-frame ATG was isolated and sequenced. The translated amino acid sequence contained 961 amino acids with a calculated molecular weight 106,665. Sequence similarities of the bovine enzyme to human and E. coli orthologs were 92 and 27%, respectively. The N-terminal amino acid sequence seemed to be a mitochondrial targeting signal. To determine the cleavage site of the signal sequence we analyzed the mature enzyme purified from bovine adrenocortical mitochondria. Analysis of CNBr-digested peptides revealed that the N-terminus was heterogeneous. We suggest that nonspecific aminopeptidase might remove several amino acids from the N-terminus after mitochondrial processing peptidase has cleaved Gly(67)-Leu(68) or Leu(68)-Trp(69).


Relationship between Serum Protein Electrophoresis, Endoscopic and Histopathological Scores in 99 Cats with Chronic Enteropathy.
Few studies have investigated total protein (TP) and serum protein electrophoresis (SPE) in cats with chronic enteropathy (CE). Cats diagnosed with CE were evaluated to investigate the relationships between TP, SPE and endoscopy, histopathology, and extraintestinal involvement. Medical records were searched for cats with a history of chronic gastrointestinal signs and a final diagnosis of CE. Information on signalment, TP, SPE, endoscopic score, histopathological diagnosis and score, and concurrent hepatic or pancreatic ultrasonographic alterations was collected. Relationships between protein profiles and other variables were investigated. Ninety-nine cats were included in the study, 63 diagnosed with various degrees of bowel inflammation and 36 with small-cell alimentary lymphoma. The most common TP alteration was hypoproteinemia (24%). No significant differences were observed between protein profiles and endoscopic and histopathological severity scores. Forty-five cats showing concurrent pancreatic and/or hepatic ultrasonographic alterations, had significantly lower albumin, lower α-globulin, and higher γ-globulin levels than cats not showing concurrent alterations. Disease severity scores did not seem to influence the protein profile in cats with CE. Extraintestinal involvement may be suspected in cats with lower albumin and α-globulins and higher γ-globulins.


A literature review on Fuchs uveitis syndrome: An update.
Fuchs uveitis syndrome is a chronic, typically unilateral, ocular condition characterized by an asymptomatic mild inflammatory syndrome that can result in cataract and secondary glaucoma. Diagnosis is largely clinical because the etiology remains obscure. Fuchs uveitis syndrome is most likely the result of different insults or pathogenic mechanisms, including infections, autoimmune diseases, hereditary and sympathetic dysfunction. According to the infectious theory, the infection of herpes simplex virus, ocular toxoplasmosis, cytomegalovirus, rubella virus, and other viruses have been implicated in the pathogenesis of the disease. There is no indication for corticosteroid therapy in Fuchs patients, and treatment should be mostly reserved to cataract and glaucoma. Phacoemulsification with intraocular lens implantation is a safe procedure with good visual outcomes in patients with Fuchs uveitis syndrome. Glaucoma is often unresponsive to treatment and should actively be monitored both preoperatively and postoperatively in these patients. We discuss the current understanding of Fuchs uveitis syndrome from its clinical presentations through recommended management and provide a comprehensive description and the updated knowledge of its pathophysiology.


Epidural morphine delays the onset of tourniquet pain during epidural lidocaine anesthesia.
We conducted a randomized, double-blinded study to examine the onset time of tourniquet pain during epidural lidocaine anesthesia either with or without morphine in the epidural solution. Forty-five patients undergoing knee surgery with a thigh tourniquet were randomly allocated into 3 groups of 15 patients each: epidural morphine (EM; epidural administration of 17 mL of 2% lidocaine plus 2 mg of morphine, followed by IV injection of 0.2 mL of normal saline), IV morphine (IVM; 17 mL of 2% lidocaine plus 0.2 mL of normal saline, followed by IVM 2 mg IV), and control (17 mL of 2% lidocaine plus 0.2 mL of normal saline, followed by 0.2 mL of normal saline IV). The onset time of tourniquet pain was recorded. The level of sensory block was determined by the pinprick method at the occurrence of tourniquet pain. Hemodynamic changes and side effects of EM were also recorded. The onset time of tourniquet pain from both the epidural injection and the tourniquet inflation were significantly longer in the EM group (103 +/- 15 min and 80 +/- 15 min, respectively) compared with the IVM group (74 +/- 12 min and 50 +/- 12 min, respectively; P < 0.05) and the Control group (67 +/- 9 min and 45 +/- 9 min, respectively; P < 0.05). The level of sensory block at the onset of tourniquet pain and hemodynamic changes were not different among the three groups. Only two and three patients in the EM group complained of nausea/vomiting and pruritus, respectively. Respiratory depression was not observed in any patient. We conclude that epidural injection of the mixture of 2 mg of morphine and 2% lidocaine solution delayed the onset of tourniquet pain during epidural lidocaine anesthesia without significant morphine-related side effects. We examined the effect of epidural morphine on the onset of tourniquet pain during epidural lidocaine anesthesia. We found that the addition of 2 mg of morphine to epidural 2% lidocaine significantly delayed the onset of tourniquet pain without increasing morphine-related side effects.


Measuring invasion in an organotypic model.
Organotypic cultures are in vitro models that can be used to study the interactions between tumour and stromal cells. Collective tumour cell invasion in organotypic assays resembles that seen in human tissues in vivo, suggesting physiological relevance. A qualitative, pathological description of such invasion may be inadequate, and there is therefore a need to accurately quantify the degree of invasion. Although the simplest method to quantify invasion is to measure maximum invasive depth, this ignores the importance of the pattern of tumour invasion, which often reflects tumour aggressiveness. We use image analysis software to analyse organotypic invasion objectively, taking into account the average depth of tumour invasion, and the number and area of invading tumour islands. The product of these parameters is termed the "invasion index," which maximises differences in invasion and also reflects the invasive pattern of the gel in a way that none of the individual parameters does alone.


Dexmedetomidine: clinical application as an adjunct for intravenous regional anesthesia.
The selective α-2 adrenoceptor agonist, dexmedetomidine, has been shown to be a useful, safe adjunct in perioperative medicine. Intravenous regional anesthesia is one of the simplest forms of regional anesthesia and has a high degree of success. However, intravenous regional anesthesia is limited by the development of tourniquet pain and its inability to provide postoperative analgesia. To improve block quality, prolong postdeflation analgesia, and decrease tourniquet pain, various chemical additives have been combined with local anesthetics, although with limited success. The antinociceptive effects of α-2 adrenoceptor agonists have been shown in animals and in humans. However, less is known about the clinical effects of dexmedetomidine when coadministered with local anesthetics in patients undergoing intravenous regional anesthesia. This review examines what is currently known to improve our understanding of the properties and application of dexmedetomidine when used as an adjunct in intravenous regional anesthesia.


Toward the Role of Language Teacher Confirmation and Stroke in EFL/ESL Students' Motivation and Academic Engagement: A Theoretical Review.
Following the recent special issue in the journal of Frontiers in Psychology, named "The Role of Teacher Interpersonal Variables in Students' Academic Engagement, Success, and Motivation," this review is carried out to describe two prime instances of teacher interpersonal behaviors, namely teacher confirmation and stroke, their underlying frameworks, and contributions to desirable student-related outcomes. In light of rhetorical-relational goal theory and the school of positive psychology, it is stipulated that language teacher confirmation and stroke are facilitators of EFL/ESL students' level of motivation and academic engagement. Providing empirical evidence, the argument regarding the pivotal role of language teacher confirmation and stroke in EFL/ESL contexts was proved. Reviewing the available literature on the aforementioned variables, some pedagogical implications were suggested for teacher trainers, educational supervisors, and pre- and in-service language teachers. Finally, the limitations and drawbacks of the reviewed studies were identified and some avenues for further research were recommended, accordingly.


Exploring the Role of Visual Design in Digital Public Health Safety Education.
In this research, the positive role of interface visual design in digital safety education was verified taking COVID-19 prevention and control knowledge as the content of public health safety education, where interface emotion (positive, negative, and neutral) and interface layout (waterfall typed and juxtaposition typed) were regarded as independent variables, and readers' understanding, course evaluation and system usability score were dependent variables. As revealed in the results of a 3 × 2 two-factor experiment in which 252 college students participated: first, different interface emotion can cause significantly different understanding, where negative emotion has the best learning transfer effect; second, due to the difference in interface emotion, participants may give certain courses significantly different evaluation scores, while positive emotional interface contributes to the obviously high scores of three course-evaluation items, "appeal of the lesson", "enjoyment of the lesson" and "interface quality"; third, significantly different system usability can be caused by different interface layout, where waterfall-type layout enjoys higher appraisal from users; fourth, interface emotion and interface layout have a similar interactive effects in terms of "effort of the lesson" and "interface quality", where waterfall-type layout is favored in terms of positive emotional interface, and juxtaposition-type layout is more advantageous in terms of negative emotional interface. These results are of vital significance for interface design and safety education. Further, the visual design method for interface emotion and interface layout were analyzed to determine the most suitable design principles so as to improve the effect of digital public health safety education and provide constructive ideas for fighting against COVID-19 at the educational level.


Effect of hydrocortisone on immune system of the lizard, Chalcides ocellatus. II. Differential action on T and B lymphocytes.
Lymphocytes of thymus, spleen, peripheral blood (PB) and bone marrow (BM) collected from adult lizards, Chalcides ocellatus were cultured for 24 hr in the presence of 10(-3)M hydrocortisone acetate (HC) in order to assess the effect of in vitro HC on lizard T and B cell viability. The results indicated that HC induced stepwise, time-dependent mortality of the majority of thymocytes carrying T cell specific antigen(s) (TSA), 30-50% of T cells of spleen, PB and BM, and of a proportion of splenic B lymphocytes. Administration of 1 mg/g body weight HC to adult Ch. ocellatus lead to depletion of all TSA+ thymocytes. In contrast, T lymphocytes in the peripheral lymphoid compartments revealed both sensitivity and resistance to HC; similarly, B lymphocytes constituted susceptible and resistant subpopulations.


Retraction: Focusing on the influence of testosterone on leptin and resistin in male hypogonads: missing link in insulin resistance?
This article released online on September 22, 2010 as advance publication was withdrawn at the request of the authors.


The use of the ketogenic diet in the treatment of psychiatric disorders.
The ketogenic diet (KD) is a high-fat, low-carbohydrate, and moderate-protein diet that has shown benefit as a treatment in neurologic disorders and may serve as a therapeutic option in individuals with psychiatric disorders. A search was conducted using EBSCOhost and PubMed databases for studies relating to ketogenic or low-carbohydrate diets and psychiatric disorders. A total of 32 experimental or observational studies were identified by initial search strategies, 14 of which met the criteria to be included in this analysis. Although specific diet formulations varied somewhat between studies, they all generally examined low-carbohydrate dietary intake with the goal of producing a ketotic state. The studies included in this review indicated the KD was beneficial in reducing symptoms associated with various psychiatric disorders. This review summarizes the available evidence regarding the efficacy of the ketogenic diet in psychiatric disease states. Data from the studies analyzed demonstrated a positive response in individuals who were able to remain on the diet, regardless of the disease state. However, there is a need for more data to clearly define the specific benefits the KD may provide.


The function of adipsin and C9 protein in the complement system in HIV-associated preeclampsia.
In preeclampsia, there are excessive complement components expressed due to increased complement activation; therefore, this study investigated the concentration of adipsin and C9 in HIV-associated preeclampsia. The study population (n = 76) was stratified by pregnancy type (normotensive pregnant and preeclampsia) and by HIV status. Serum was assayed for the concentration of adipsin and C9 using a Bioplex immunoassay procedure. Maternal weight did not differ (p = 0.1196) across the study groups. The concentration of adipsin was statistically different between the PE vs normotensive pregnant groups, irrespective of HIV status (p = 0.0439). There was no significant difference in adipsin concentration between HIV-negative vs HIV-positive groups, irrespective of pregnancy type (p = 0.6290). Additionally, there was a significant difference in adipsin concentration between HIV-negative normotensive vs HIV-negative preeclampsia (p < 0.05), as well as a difference between HIV-negative preeclampsia vs HIV-positive preeclampsia (p < 0.05). C9 protein expression was not statistically different between the normotensive and PE groups, regardless of HIV status (p = 0.5365). No statistical significance in C9 expression was found between HIV-positive vs HIV-negative groups, regardless of pregnancy type (p = 0.3166). Similarly, no statistical significance was noted across all study groups (p = 0.0774). This study demonstrates that there is a strong correlation between the up-regulation of adipsin and PE and that adipsin is a promising biomarker to use as a diagnostic tool for PE.


Relationship between the biodegradative capability of soil micromycetes for pentachlorophenol and for pentachloronitrobenzene.
A collection of 1056 strains in our laboratory were incubated with various xenobiotics among which were two potent fungicides: pentachlorophenol (PCP) and pentachloronitrobenzene (PCNB). The production of extracellular phenoloxidases were examined, using a series of ten different reagents. On the whole, PCNB is less accessible to fungal degradation than PCP. Although no correlation was found between the biodegradative capability of individual fungal strains for PCP or for PCNB, when taxonomic groups were considered as a whole, the same activity profiles were found. Zygomycetes were the most efficient; yeasts the least efficient towards both substrates. A more detailed study of the metabolism of both substrates on selected strains is in progress.


Joule-Thomson Effect on a CCS-Relevant (CO2 + N2) System.
The Joule-Thomson effect is a key chemical thermodynamic property that is encountered in several industrial applications for CO2 capture and storage (CCS). An apparatus was designed and built for determining the Joule-Thomson effect. The accuracy of the device was verified by comparing the experimental data with the literature on nitrogen and carbon dioxide. New Joule-Thomson coefficient (μJT) measurements for three binary mixtures of (CO2 + N2) with molar compositions x N2 = (0.05, 0.10, 0.50) were performed in the temperature range between 298.15 and 423.15 K and at pressures up to 14 MPa. Three equations of state (GERG-2008 equation, AGA8-92DC, and the Peng-Robinson) were used to calculate the μJT compared with the corresponding experimental data. All of the equations studied here except PR have shown good prediction of μJT for (CO2 + N2) mixtures. The relative deviations with respect to experimental data for all (CO2 + N2) mixtures from the GERG-2008 were within the ±2.5% band, and the AGA8-DC92 EoSs were within ±3%. The Joule-Thomson inversion curve (JTIC) has also been modeled by the aforementioned EoSs, and a comparison was made between the calculated JTICs and the available literature data. The GERG-2008 and AGA8-92DC EoSs show good agreement in predicting the JTIC for pure CO2 and N2. The PR equation only matches well with the JTIC for pure N2, while it gives a poor prediction for pure CO2. For the (CO2 + N2) mixtures, the three equations all give similar results throughout the full span of JTICs. The temperature and pressure of the transportation and compression conditions in CCS are far lower than the corresponding predicted P inv,max and T inv,max for (CO2 + N2) mixtures.


Choosing a beverage: comparison of preferences and beliefs related to the reported consumption of regular vs. diet sodas.
In a survey conducted among American females (N = 100, mean age = 20.8 years), consumption of regular and diet sodas and related beliefs and concerns were measured. Based on reported frequencies of consumption, 30 could be classified as users of regular and 44 as users of diet sodas, while 20 subjects did not use either. Both user groups reported liking for their "own" sodas and dislike for the "other" sodas, and non-users did not like either. Beliefs best differentiating among the three groups were: (1) superiority of taste of their "own" sodas, (2) perceived efficiency to quench thirst, and (3) perceived compatibility with other menu items. Users of diet sodas and the non-users were more concerned about weight-related issues than users of regular sodas, who had less concerned attitudes. The users of regular sodas also reported a significantly higher frequency of consumption of several foods high in sugar, fat and/or sodium. Thus, the selection of one's principal soda is not only a choice between two beverages but may be an indication of a particular consumption style and reflect a whole set of attitudes towards one's own body.


Cortical Motor Planning and Biomechanical Stability During Unplanned Jump Landings in Men With Anterior Cruciate Ligament Reconstruction.
Athletes with anterior cruciate ligament (ACL) reconstruction (ACLR) exhibit increased cortical motor planning during simple sensorimotor tasks compared with healthy athletes serving as control groups. This may interfere with proper decision making during time-constrained movements, elevating the reinjury risk. To compare cortical motor planning and biomechanical stability during jump landings between participants with ACLR and healthy individuals. Cross-sectional study. Laboratory. Ten men with ACLR (age = 28 ± 4 years, time after surgery = 63 ± 35 months) and 17 healthy men (age = 28 ± 4 years) completed 43 ± 4 preplanned (landing leg shown before takeoff) and 51 ± 5 unplanned (visual cue during flight) countermovement jumps with single-legged landings. Movement-related cortical potentials (MRCPs) and frontal θ frequency power before the jump were analyzed using electroencephalography. Movement-related cortical potentials were subdivided into 3 successive 0.5-second time periods (readiness potential [RP]-1, RP-2, and negative slope [NS]) relative to movement onset, with higher values indicating more motor planning. Theta power was calculated for the last 0.5 second before movement onset, with higher values demonstrating more focused attention. Biomechanical landing stability was measured via peak vertical ground reaction force, time to stabilization, and center of pressure. Both the ACLR and healthy groups evoked MRCPs at all 3 time periods. During the unplanned task analyzed using P values and Cohen d, the ACLR group exhibited slightly higher but not different MRCPs, achieving medium effect sizes (RP-1: P = .25, d = 0.44; RP-2: P = .20, d = 0.53; NS: P = .28, d = 0.47). The ACLR group also showed slightly higher θ power values that were not different during the preplanned (P = .18, d = 0.29) or unplanned (P = .42, d = 0.07) condition, achieving small effect sizes. The groups did not differ in their biomechanical outcomes (P values > .05). No condition × group interactions occurred (P values > .05). Our jump-landing task evoked MRCPs. Although not different between groups, the observed effect sizes provided the first indication that men with ACLR might have consistently relied on more cortical motor planning associated with unplanned jump landings. Confirmatory studies with larger sample sizes are warranted.


A comparison of real-world effectiveness of vortioxetine along the treatment algorithm for major depressive disorder.
To evaluate the effectiveness of vortioxetine in major depressive disorder (MDD) when used as a first-line versus second-line treatment or later. This was a post-hoc analysis of three 3-month non-interventional, prospective studies of vortioxetine in MDD - REVIDA (Malaysia, Philippines, Singapore, Thailand), PREVIDA (Pakistan) and TREVIDA (Taiwan). Improvements in depressive symptoms (PHQ-9, CGI-S), cognitive function (PDQ-D) and work productivity (WPAI) were compared between studies, and in a pooled analysis of patients using vortioxetine as the first line versus second-line treatment or later. Safety was compared between studies. Overall, 798 patients were analyzed (PREVIDA = 425, REVIDA = 130, TREVIDA = 243). Most patients in PREVIDA (60.5%)/REVIDA (57.4%) used vortioxetine as first-line treatment versus TREVIDA (21.8%). Generally, greater improvements from baseline were observed across outcome measures in PREVIDA/REVIDA versus TREVIDA (Month 3, p < .0001). Vortioxetine as first-line treatment was associated with greater improvements in depression severity, cognition, functioning outcomes compared to second-line or later users (PHQ-9: -16.1 [6.4] vs -10.8 [8.9]; CGI-S: -2.7 [1.1] vs -2.0 [1.4]; PDQ-D: -29.5 [17.7] vs -18.5 [21.4]; p < .0001 at Month 3) as well as greater response (PHQ-9: 88.6% vs 61.5%; p < .0001) and remission rates (PHQ-9: 75.4% vs 47.7%; p < .0001). No new adverse events were reported outside of the product label. In the Asian real-world setting, vortioxetine showed greater improvements in depressive and cognitive symptoms, work functioning, and response and remission rates when used as first-line versus second-line treatment or later. Vortioxetine was well-tolerated irrespective of the study population across Asia.


RIPK3 controls MAIT cell accumulation during development but not during infection.
Cell death mechanisms in T lymphocytes vary according to their developmental stage, cell subset and activation status. The cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are largely unknown. Here we report that MAIT cells express key necroptotic machinery; receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) protein, in abundance. Despite this, we discovered that the loss of RIPK3, but not necroptotic effector MLKL or apoptotic caspase-8, specifically increased MAIT cell abundance at steady-state in the thymus, spleen, liver and lungs, in a cell-intrinsic manner. In contrast, over the course of infection with Francisella tularensis, RIPK3 deficiency did not impact the magnitude of the expansion nor contraction of MAIT cell pools. These findings suggest that, distinct from conventional T cells, the accumulation of MAIT cells is restrained by RIPK3 signalling, likely prior to thymic egress, in a manner independent of canonical apoptotic and necroptotic cell death pathways.


Indirect costs related to caregivers' absence from work after paediatric tonsil surgery.
Tonsillotomy has gradually replaced tonsillectomy as the surgical method of choice in children with upper airway obstruction during sleep, because of less postoperative pain and a shorter recovery time. The aim of this study was to examine the costs related to caregivers' absenteeism from work after tonsillectomy (TE) and tonsillotomy (TT). All tonsillectomies and tonsillotomies in Sweden due to upper airway obstruction during 1 year, reported to the National Tonsil Surgery Register in children aged 1-11 were included, n = 4534. The number of days the child needed analgesics after surgery was used as a proxy to estimate the number of work days lost for the caregiver. Data from the Social Insurance Agency (Försäkringskassan) regarding the days the parents received temporary parental benefits in the month following surgery were also analysed. The indirect costs due to the caregivers' absenteeism after tonsillectomy vs tonsillotomy were calculated, using the human capital method. The patient-reported use of postoperative analgesic use was 77% (n = 3510). Data from the Social Insurance Agency were gathered for all 4534 children. The mean duration of analgesic treatment was 4.6 days (indirect cost of EUR 747). The mean number of days with parental benefits was 2.9 (EUR 667). The indirect cost of tonsillectomy was 61% higher than that of tonsillotomy (EUR 1010 vs EUR 629). The results show that the choice of surgical method affects the indirect costs, favouring the use of tonsillotomy over tonsillectomy for the treatment of children with SDB, due to less postoperative pain.


The relation of oxygen intake and velocity of walking and running, in competition walkers.
1. The oxygen intake of four Olympic walkers was measured while walking and running at varying velocities on a treadmill at an altitude of 1800 m.2. The relation between O(2) intake and running at speeds between 8 km/hr and 21 km/hr was linear. The relation for walking at speeds up to 8 km/hr followed an upward concave curve. These findings were similar to results obtained at sea level by other investigators.3. For walking at speeds between 8 km/hr and 14.5 km/hr the relation of O(2) intake and velocity was a straight line having a slope twice that of running.4. Maximum O(2) intake in walking averaged 60.0 ml./kg/min (range 55.8-64.1 ml./kg/min) compared with 57.4 ml./kg/min (range 55.2-60.2 ml./kg/min) in running. An international class long distance runner serving as a control reached a maximum O(2) intake of 70 ml./kg/min.


Structural analysis of factors related to FAM3C/ILEI dimerization and identification of inhibitor candidates targeting cancer treatment.
FAM3 is a superfamily of four cytokines that maintain a single globular structure β -β -α of three classes: FAM3A, B, C and D. FAM3C was the first member of this family related to cancer and is functionally characterized as an essential factor for the epithelial-mesenchymal transition (EMT), leading to late delays in tumor progression. Due to its crucial role in EMT and metastasis, FAM3C has been termed an interleukin-like EMT (ILEI) inducer. There are several studies on the part of FAM3C in the progression of cancer and other diseases. However, little is known about its cellular receptors and possible inhibitors. In this study, based on in silico approaches, we performed structural analyses of factors related to FAM3C/ILEI dimerization. We also identified four possible inhibitor candidates, expected to be exciting prototypes and could be submitted to future biological tests targeting cancer treatment.


Cold water reduces the severity of parasite-inflicted damage: support for wintertime recuperation in aquatic hosts.
The reduction in host fitness caused by parasite infections (virulence) depends on infection intensity and the degree of damage caused per parasite. Environmental conditions can shape both virulence components, but in contrast to infection intensity, environmental impacts on per-parasite damage are poorly understood. Here, we studied the effect of ambient temperature on per-parasite damage, which is jointly determined by the ability of parasites to induce harm (per-parasite pathogenicity) and the ability of hosts to limit damage (tolerance). We experimentally exposed two salmonid species, Atlantic salmon (Salmo salar) and sea trout (Salmo trutta), to replicated genotypes of the eye fluke Diplostomum pseudospathaceum. After development of health damage (eye cataracts) in warm water (16 °C) during the first 12 weeks post exposure, we maintained the fish at either 5 °C (cold water) or 16 °C for another 8 weeks and quantified changes in cataracts as a function of parasite load. We found that per-parasite damage was reduced in cold compared to warm water, suggesting that cold temperatures improved host health. Per-parasite damage was also affected by parasite genotype and host species, but these effects did not change with temperature. Our findings suggest that cold-water seasons, which are often neglected in host-parasite studies due to low infection risk, could allow hosts to recuperate and thus, may have important implications for the ecology and epidemiology of parasite infections.


Voltage gradients and microtubules both involved in intercellular protein and mitochondria transport in the telotrophic ovariole of Dysdercus intermedius.
In the telotrophic ovariole of Dysdercus intermedius the intercellular transport consists of different subsystems. Microinjection of FITC-labeled slowly diffusing proteins with opposite electrical net charges and of mitochondria was used to study the translocation of macromolecules and organelles. a) By intracellular measurements a voltage gradient of about 4 mV between the tropharium as the more negative side and the previtellogenic oocytes could be demonstrated. b) After injection into the tropharium negatively charged proteins migrated according to the electropotential gradient via the trophic cords into the oocytes. Positively charged proteins, however, were retained in the tropharium. c) After injection into previtellogenic oocytes both negatively and positively charged proteins moved into the trophic cords. Thus, the effectiveness of the electropotential gradient on the distribution of charged proteins is more pronounced from the tropharium side. d) Mitochondria microinjected into the trophic core were probably aligned along microtubules and translocated towards the trophic cords. - These results suggest that in the telotrophic bug ovariole a number of intercellular transport subsystems contribute to provide previtellogenic oocytes with nurse cells products. An electrophoretic transport mechanism for soluble proteins acting especially within the tropharium and a microtubule-associated transport for mitochondria could be evidenced.


Attempts to produce Theileria parva-infected mouse cells using cell fusion techniques.
Ehrlich ascites tumour (EAT) cells were fused with Theileria parva-infected bovine lymphoid (C2) cells using inactivated Sendai virus. A variety of techniques were employed to try and increase fusion percentage and harvest of heterokaryons. There was no evidence that pre-exposure of C2 cells to Sendai virus or phytohaemagglutinin improved fusion percentage, but the percentage was higher when 10(8) C2 cells were fused with 10(7) EAT cells, as compared with a ratio of 10(7) C2: 10(6) EAT. An increased yield of multinucleate cells was obtained using a calf serum gradient to separate cells of different sizes. An attempt to fuse EAT cells with free macroschizonts was not sucessful. When cells were grown in hypoxanthine/aminopterin/thymidine medium (HAT), T parva appeared to be selectively killed by the aminopterin present; this finding would seem to militate against the use of a HAT selection system to clone parasitised hybrids. C2 cells could be selected out by passage of mixed cultures through mice, but no evidence of parasitosis was detected in EAT cells which became established.


Effect of inotropic and vasodilator therapy on left ventricular diastolic filling in dogs with severe left ventricular dysfunction.
Inotropic and vasodilator therapy for congestive heart failure improve left ventricular systolic performance by different mechanisms. However, the nature and extent to which diastolic filling is altered have not been well described. Acute severe left ventricular dysfunction was induced in 21 dogs by severe left ventricular global ischemia produced by left main coronary artery microsphere embolization until left ventricular end-diastolic pressure was greater than or equal to 18 mm Hg. Dobutamine was infused in seven dogs until the peak positive first derivative of left ventricular pressure (dP/dt) increased by greater than or equal to 33%. Nitroprusside was infused in seven dogs until left ventricular end-diastolic pressure was less than 15 mm Hg. Seven dogs were observed for 1 h after the induction of acute severe left ventricular dysfunction and served as the control group. In all groups of dogs, severe left ventricular dysfunction resulted in left ventricular dilation, reduction in area ejection fraction, elevation of left ventricular end-diastolic pressure and an early redistribution of diastolic filling (increased 1/3 and 1/2 filling fractions) despite a markedly abnormal time constant of relaxation. No changes were noted in any variable after 1 h of observation in the seven control dogs. Nitroprusside reduced left ventricular size and filling pressure, increased cardiac output, improved relaxation and redistributed diastolic filling to later in diastole as characterized by a reduced 1/3 filling fraction (19.4 +/- 7.4% versus 51.4 +/- 10%, p less than 0.001). The pressure-area curve was shifted downward and leftward.(ABSTRACT TRUNCATED AT 250 WORDS)


Dried human cultured epidermis accelerates wound healing in diabetic mouse skin defect wounds.
Cryopreserved allogeneic cultured epidermis (CE) is used for treating second-degree burn wounds and diabetic foot ulcers; however, the need for cryopreservation limits its use. We have previously reported that CE accelerates wound healing irrespective of its viability and hypothesized that dehydrated CEs lacking living cells may act as an effective wound dressing. We prepared dried CE and investigated its morphological and physical properties and wound-healing effects and compared them with those of cryopreserved CE. Hematoxylin-eosin staining, immunostaining for basement membrane, and electron microscopy revealed that the morphologies of dried CE and cryopreserved CE were comparable and that the membrane structure was not damaged. The breaking strength, modulus of elasticity, and water permeability of dried CE were comparable with those of the cryopreserved CE. Furthermore, the levels of various active cytokines and chemokines in dried CE were comparable with those in cryopreserved CE. Dried CE applied to skin defect in diabetic mice significantly reduced the wound area and increased the new epithelium length 4 and 7 days after implantation, similar to that observed for cryopreserved CE. Consequently, dried CE had similar morphological and physical properties and wound-healing effects compared with those of cryopreserved CE and can be a physiological and versatile wound-dressing.


A systematic approach to reduce intraocular pressure for the treatment of glaucoma.
Glaucoma is the leading cause of irreversible blindness due to increased intraocular pressure (IOP) in the eye. We have developed a novel treatment option for glaucoma based on a real-time IOP-dependent nitric oxide synthase (NOS) and packed in a therapeutic contact lens to reduce the IOP. First, 1.6 nmole nitric oxide was produced from the genetic chassis, which was optimized for isopropyl β-d-1-thiogalactopyranoside (IPTG) induction in a T7 expression system. For biosafety concerns to human being, the csgAD genes responsible for curli biofilm formation in Escherichia coli were co-expressed with NOS in the designated NOSAD strain to strengthen the adherence of cells to the contact lens, thereby preventing the contamination into the eyes. Moreover, NOSAD is a diaminopimelic acid (DAP) auxotrophic strain, which cannot survive without supplementation of DAP and reached the critical consideration of biosafety to the environment. We also demonstrated that the nitric oxide diffusion was 3.6-times enhanced from penetration into the aqueous humor of porcine eyes. The deformation ratio of the contact lens was correlated to the change of IOP by using a digital image correlation (DIC) system in a porcine eye model. The novel systematic approach provides an alternative treatment for glaucoma patients in the future.


Diagnosis and classification of atrial septal aneurysm by two-dimensional echocardiography: report of 80 consecutive cases.
Atrial septal aneurysms have been related (either by association or as potential causes) to systolic clicks, atrial arrhythmias, systemic and pulmonary embolism, atrioventricular valve prolapse and atrial septal defect. To study these associations and the incidence of atrial septal aneurysm, we reviewed 80 consecutive patients (female to male ratio 1.9:1, mean age 47 years, range 1 day to 89 years) who had been identified prospectively as having an atrial septal aneurysm. These were found in 36,200 two-dimensional echocardiographic studies (incidence: 0.22% overall; 0.29% in the last year of the study done between 1978 and 1984). Three types of fossa ovalis aneurysm and one type of aneurysm involving the entire atrial septum were observed; a fossa ovalis aneurysm with leftward projection and excursion of less than 5 mm or an aneurysm involving the entire atrial septum with rightward projection was not observed. Atrial septal aneurysm occurred more often as an isolated abnormality than in association with other cardiac malformations, although all patients with an aneurysm involving the entire atrial septum had complex congenital cardiac anomalies of the hypoplastic right heart type. The reported associations between atrial septal aneurysms and atrial septal defect, atrioventricular valve prolapse, midsystolic clicks, atrial arrhythmias and cerebral ischemic events were examined. A hypothesis based on interatrial pressure gradients is proposed to explain the different motions and configurational characteristics of fossa ovalis aneurysms observed in these patients. All patients in whom atrial septal aneurysm is demonstrated should undergo examination for atrial septal defect. Atrial septal aneurysm should be specifically looked for in patients who have these associations and who undergo two-dimensional echocardiography, especially if these abnormalities are unexplained.


Asiatic acid alleviates liver fibrosis via multiple signaling pathways based on integrated network pharmacology and lipidomics.
Liver fibrosis is characterized by the abnormal deposition of the extracellular matrix with a severe inflammatory response and/or metabolic disorder. Asiatic acid (AA), a natural compound derived from Centella asiatica, exhibited potent anti-fibrosis effects. This investigation first confirmed the anti-fibrosis effects of AA in TGF-β-LX-2 cells and CCl4-induced liver fibrosis mice, and then sought to elucidate a novel mechanism of action by integrating network pharmacology and lipidomics. Network pharmacology was used to find potential targets of AA, while lipidomics was used to identify differential metabolites between fibrosis and recovered cohorts. AA could suppress hepatic stellate cell activation in vitro and improve liver fibrosis in vivo. Network pharmacology unveiled the genes involved in pathways in cancer, peroxisome proliferators-activated receptors signaling pathway, and arachidonic acid metabolism pathway. Furthermore, five key genes were found in the both human and mouse databases, indicating that arachidonic acid metabolism was important. Changes in lyso-phosphocholine (22:5), prostaglandin F2α, and other related lipid metabolites also suggested the involvement of arachidonic acid metabolism the anti-fibrotic effect. In summary, our integrated strategies demonstrated that AA targeted multiple targets and impeded the progression of liver fibrosis by ameliorating arachidonic acid metabolism.


Traumatic Brain Injury Mortality and Correlates in Low- and Middle-Income Countries: A Meta-Epidemiological Study.
It is estimated that up to 69 million people per year experience traumatic brain injury (TBI) with the highest prevalence found in low- and middle-income countries (LMICs). A paucity of data suggests that the mortality rate after severe TBI is twice as high in LMICs than in high-income countries. To analyze TBI mortality in LMICs and to evaluate what country-based socioeconomic and demographic parameters influence TBI outcomes. Four databases were searched for the period January 1, 2002, to January 1, 2022, for studies describing TBI outcomes in LMICs. Multivariable analysis was performed using multivariable linear regression, with the outcome as the pooled mortality by country and the covariates as the adjusted parameters. Our search yielded 14 376 records of which 101 were included in the final analysis, totaling 59 197 patients and representing 31 LMICs. The pooled TBI-related mortality was 16.7% (95% CI: 13.7%-20.3%) without significant differences comparing pediatrics vs adults. Pooled severe TBI-related mortality was significantly higher than mild. Multivariable analysis showed a significant association between TBI-related mortality and median income ( P = .04), population percentage below poverty line ( P = .02), primary school enrollment ( P = .01), and poverty head ratio ( P = .04). TBI-related mortality in LMICs is 3-fold to 4-fold higher than that reported in high-income countries. Within LMICs, parameters associated with poorer outcomes after TBI include factors recognized as social determinants of health. Addressing social determinants of health in LMICs might expedite the quest to close the care delivery gap after TBI.


Exercise Tolerance in Patients Treated With a Durable Left Ventricular Assist Device: Importance of Myocardial Recovery.
The number of patients supported with left ventricular assist devices (LVADs) is growing and support times are increasing. This has led to a greater focus on functional capacity of these patients. LVADs greatly improve heart failure symptoms, but surprisingly, improvement in peak oxygen uptake (pVO2) is small and remains decreased at approximately 50% of normal values. Inadequate increase in cardiac output during exercise is the main responsible factor for the low pVO2 in LVAD recipients. Some patients experience LV recovery during mechanical unloading and these patients have a higher pVO2. Here we review the various components determining exercise cardiac output in LVAD recipients and discuss the potential impact of cardiac recovery on these components. LV recovery may affect several components, leading to improved hemodynamics during exercise and, in turn, physical capacity in patients with advanced heart failure undergoing LVAD implantation.


A phase II clinical trial evaluating the use of two sequential, four-drug combination chemotherapy regimens in ambulatory bronchogenic adenocarcinoma patients.
Forty-three ambulatory patients with locally advanced or metastatic bronchogenic adenocarcinoma were sequentially treated with two potentially mutually non-cross-resistant chemotherapy regimens. A new regimen, MVPF (mitomycin-c, vinblastine, procarbazine, and 5-fluorouracil), was given until progressive disease occurred. Then, a second regimen--MOCC (methotrexate, vincristine [Oncovin], cyclophosphamide, and CCNU)--was initiated. At further progression, regional disease patients received radiotherapy, whereas extensive disease patients received Phase II agents. Of the 43 patients entered on the study, 40 were evaluable. Three patients withdrew early due to poor tolerance of the regimen. The response rate for MVPF was 33% (12 of 40 PR, 1 of 40 CR) compared to a 4% (1 of 23 PR) response for MOCC (difference: p < or = .03), for a total response rate of 35%. Although there was an initial improvement in survival for responders (31.7 weeks) versus nonresponders (15.7 weeks) at the 75th percentile (p < or = .05), there was no significant difference in median survival. The hematologic toxicity was equivalent for both groups, whereas nonhematologic toxicity revealed a high incidence of nausea and vomiting in the MVPF group. It is concluded that this approach lent itself well to ambulatory care, and MVPF could be considered an alternative to cyclophosphamide-based regimens. However, the absence of a meaningful CR rate and lack of influence of response on median survival were factors limiting its effectiveness.


Serum immunoglobulin M, G, and A concentration levels in Turner's syndrome compared with normal women and men.
Serum concentrations of immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) were determined in 15 women with a lack of X chromsome material (Turner's syndrome), and compared with the immunoglobulin concentrations in normal men and women. Further, the investigation is supplemented by a comparison of normal women and the Turner group matched according to age. The serum concentrations of IgG and IgA in women with Turner's syndrome were very close to the concentration in serum from normal men, whereas the concentration of IgM was significantly lower. Compared to normal women the concentrations of IgG and IgM were significantly lower, and the concentration of IgA significantly higher in the Turner group. Whether these differences in serum immunoglobulins are determined by hormonal factors or under direct genetic control linked to the X chromosomes, is discussed.


Assessing urban flooding risk in response to climate change and urbanization based on shared socio-economic pathways.
Global climate change and rapid urbanization, mainly driven by anthropogenic activities, lead to urban flood vulnerability and uncertainty in sustainable stormwater management. This study projected the temporal and spatial variation in urban flood susceptibility during the period 2020-2050 on the basis of shared socioeconomic pathways (SSPs). A case study in Guangdong-Hong Kong-Macao Greater Bay Area (GBA) was conducted for verifying the feasibility and applicability of this approach. GBA is predicted to encounter the increase in extreme precipitation with high intensity and frequency, along with rapid expansion of constructed areas, resulting in exacerbating of urban flood susceptibility. The areas with medium and high flood susceptibility will be expected to increase continuously from 2020 to 2050, by 9.5 %, 12.0 %, and 14.4 % under SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios, respectively. In terms of the assessment of spatial-temporal flooding pattern, the areas with high flood susceptibility are overlapped with that in the populated urban center in GBA, surrounding the existing risk areas, which is consistent with the tendency of construction land expansion. The approach in the present study will provide comprehensive insights into the reliable and accurate assessment of urban flooding susceptibility in response to climate change and urbanization.


[The age-related structure of an Ixodes ricinus population studied by using a rapid anatomical method].
A rapid anatomic method for the assessment of the physiologic age of ticks and their virtual age was used in studies of the age structure of a natural population of I. ricinus in the Moscow region. The anatomic method was found quite fit for the purpose. The findings evidence that the age structure of I. ricinus (active imago) population is heterogeneous with variously directed seasonal fluctuations. In spring the structure is the youngest (up to 60% of imagoes are in the second age, 8 months) and in the fall the females are mainly old, just starting to get younger (up to 90% are in the third and fourth ages, that is, aged a year). The structure is liable to changes with seasons and years. Geographic differences in the age structures were revealed: in the fall the Moscow region population is generally older than that of the St. Petersburg region. The anatomic method widens the potentialities of studying the age structure of the populations of tick-borne encephalitis vectors.


Complete genome sequence of a novel toti-like virus from the plant-pathogenic oomycete Phytophthora cactorum.
This report describes the complete genome sequence of a double-stranded RNA (dsRNA) virus infecting the oomycetous plant pathogen Phytophthora cactorum. The virus genome consists of a single dsRNA segment of 5699 bp with two open reading frames predicted to overlap with each other and encoding a putative capsid protein of 705 aa and an RNA-dependent RNA polymerase of 779 aa. Sequence comparisons indicated that this virus, designated as "Phytophthora cactorum RNA virus 1" (PcRV1), shares the highest sequence similarity with the unclassified Pythium splendens RNA virus 1 (58% RdRp aa sequence identity). Phylogenetic analysis revealed that these two oomycete viruses group together with Giardia lamblia virus (GVL; family Totiviridae) and several unclassified toti-like viruses from arthropods, fish and fungi. This is the first report of a toti-like virus in a member of the genus Phytophthora and the first virus characterized in P. cactorum.


Infection and transformation of mouse cells by human adenovirus type 2.
The susceptibilities of C57Bl/6J mouse embryo fibroblasts (MEF) and baby mouse kidney (BMK) cells to infection or transformation by adenovirus type 2 have been compared to those of rat embryo fibroblasts (REF). Both MEF and BMK cells were some 10-fold less permissive to replication of the virus than were REF cells, even though similar fractions of all three cell types, a maximum of 50-60%, produced viral tumor and structural antigens. This observation suggests that a very late step in adenovirus production, such as assembly or maturation, occurs much less efficiently in mouse cells than it does in rat cells. No significant differences in the frequencies of transformation, as assayed by the appearance of foci of morphologically transformed cells, were observed following transfection of adenovirus type 2 or type 5 DNA into the three cell types. However, it proved extremely difficult to establish permanent lines of adenovirus-transformed mouse cells: only 2 of more than 100 attempts were successful, compared to a success rate of close to 100% with adenovirus type 2-transformed REF or SV40-transformed MEF or BMK cells. The two lines of type 2 adenovirus-transformed MEF that were established have been shown to retain and express viral genetic information.


Superoxide generated in the chloroplast stroma causes photoinhibition of photosystem I in the shade-establishing tree species Psychotria henryi.
Our previous studies indicated that high light induced significant photoinhibition of photosystem I (PSI) in the shade-establishing tree species Psychotria henryi. However, the underlying mechanism has not been fully clarified. In the present study, in order to investigate the mechanism of PSI photoinhibition in P. henryi, we treated detached leaves with constant high light in the presence of methyl viologen (MV) or a soluble α-tocopherol analog, 2,2,5,7,8-pentamethyl-6-chromanol (PMC). We found that MV significantly depressed photochemical quantum yields in PSI and PSII when compared to PMC. On condition that no PSI photoinhibition happened, although cyclic electron flow (CEF) was abolished in the MV-treated samples, P700 oxidation ratio was maintain at higher levels than the PMC-treated samples. In the presence of PMC, PSI photoinhibition little changed but PSII photoinhibition was significantly alleviated. Importantly, PSI photoinhibition was largely accelerated in the presence of MV, which stimulates the production of superoxide and subsequently other reactive oxygen species at the chloroplast stroma by accepting electrons from PSI. Furthermore, MV largely aggravated PSII photoinhibition when compared to control. These results suggest that high P700 oxidation ratio cannot prevent PSI photoinhibition in P. henryi. Furthermore, the superoxide produced in the chloroplast stroma is critical for PSI photoinhibition in the higher plant P. henryi, which is opposite to the mechanism underlying PSI photoinhibition in Arabidopsis thaliana and spinach. These findings highlight a new mechanism of PSI photoinhibition in higher plants.


Use of severity adjusted comparative systems in the development of critical pathways.
This paper has been prepared to present how South Shore Hospital has successfully used computerized applications to provide the highest quality patient care in the most cost-efficient manner.


Protective effect of resveratrol against cisplatin-induced ototoxicity in HEI-OC1 auditory cells.
Cisplatin is an effective chemotherapeutic drug, but it generates reactive oxygen species (ROS) that induce severe adverse effects such as ototoxicity. Resveratrol reportedly prevents oxidative stress-induced cell death. Thus, we hypothesized that the anti-oxidative effect of resveratrol could protect against cisplatin-induced ototoxicity. The present study examined the protective effect of resveratrol against cisplatin-induced ototoxicity in HEI-OC1 auditory cells. HEI-OC1 cells were pretreated with resveratrol at 1μM for 24h and then exposed to 15μM cisplatin for 48h. Resulting cytotoxicity was measured by the MTT method, and intracellular ROS was measured using flow cytometry. Protective effect of resveratrol was compared with other anti-oxidants. Pretreatment with resveratrol 1μM protected HEI-OC1 auditory cells against cisplatin-induced cytotoxicity and significantly reduced a cisplatin-induced increase in ROS. Resveratrol provided significant protection against 15μM cisplatin applied for 48h (50.8% cell viability in the cisplatin group vs. 57.6% in the cisplatin-plus-resveratrol group), and there was a 9% decrease in cisplatin-induced ROS associated with resveratrol. This is the study investigating the protective effects of resveratrol against cisplatin-induced ototoxicity in an auditory cell line. Resveratrol significantly reduced a cisplatin-induced increase in ROS and thereby inhibited cisplatin-induced cytotoxicity.


Improved cytosolic delivery of macromolecules through dimerization of attenuated lytic peptides.
Intracellular delivery of biomacromolecules is a challenging research field in chemical biology and drug delivery. We previously reported a peptide named L17E, which successfully delivered functional proteins, including antibodies, into cells. However, relatively high concentrations of L17E and proteins are needed. In this study, we prepared dimers of L17E and its analog L17E/Q21E. Dimerization of L17E increased cytotoxicity leading to reduced intracellular delivery compared with L17E. On the other hand, the dimers of the L17E analog, L17E/Q21E, especially when tethered at the N-termini, yielded a comparable level of intracellular delivery with L17E at decreased amounts of delivery peptides and cargoes.