EVALUATION OF PLASMA 25-HYDROXYVITAMIN D, IONIZED CALCIUM, AND PARATHYROID HORMONE IN GREEN SEA TURTLES (CHELONIA MYDAS) EXPOSED TO DIFFERENT INTENSITIES OF ULTRAVIOLET B RADIATION.
For many reptile species, adequate ultraviolet B (UVB) radiation is essential for proper calcium metabolism. In this study, the effects of UVB radiation on calcium metabolism were evaluated in green sea turtles (Chelonia mydas). 25-Hydroxyvitamin D, parathyroid hormone (PTH), and ionized calcium (iCa) were measured in juvenile (n = 18, 9 indoor, 9 outdoor) and adult (n = 8, 4 indoor, 4 outdoor) turtles. All animals were fed an identical diet. Outdoor animals had access to unfiltered sunlight, whereas indoor animals were housed under artificial lighting without UVB. Mean values for 25-hydroxyvitamin D for the outdoor and indoor groups were 34.33 ± 7.98 nmol/L and 7.11 ± 1.69 nmol/L for juveniles and 73.25 ± 30.34 nmol/L and 14.0 ± 11.52 nmol/L for adults respectively. Mean values for iCa for the outdoor and indoor groups were 0.98 ± 0.07 mmol/L and 0.99 ± 0.06 mmol/L for juveniles and 1.18 ± 0.22 mmol/L and 0.97 ± 0.18 mmol/L for adults respectively. UVB exposure (P < 0.001) and age (P < 0.001) had a significant effect on 25-hydroxyvitamin D as well as a significant interaction between the two variables (P = 0.008), with highest values in adult outdoor turtles. There was a significant interaction between age group and UVB status for iCa (P = 0.036), with greater values in older outdoor turtles. 25-Hydroxyvitamin D and total calcium were positively correlated, rs = 0.39, P = 0.042. iCa and calcium-to-phosphorus ratios were also positively correlated, rs = 0.42, P = 0.027. These results suggest that UVB exposure is an important source of 25-hydroxyvitamin D for green sea turtles and has significant effects on calcium metabolism in this species. PTH values in this study were near the minimum limits of detection and suggest that current mammalian-based PTH assays are not valid for reptiles.


A tympanometric comparison of tympanoplasty with cartilage palisades or fascia after surgery for tensa cholesteatoma in children.
The aim of the present study is to compare the tympanometric and functional findings of cartilage palisade tympanoplasty with those of tympanoplasty with temporalis fascia grafting after one-stage surgery in children with tensa cholesteatoma. In children aged 5 to 15 years (mean, 9.5 years) with tensa cholesteatoma, cartilage palisade tympanoplasty was performed in 32 ears and fascia tympanoplasty in 29 ears. Tympanometry was performed in 31 ears with cartilage palisade tympanoplasty (the palisade group) and 28 ears with fascia tympanoplasty (the fascia group) at follow-up a median of 48 months after surgical removal of the cholesteatoma (range, 3-75 months). Postoperative perforations, tympanometric parameters (tympanogram type, compliance, tympanometric width), and hearing. All postoperative re-perforations occurred in the fascia group. However, there was no difference between the palisade group and the fascia group in terms of tympanometric parameters, nor between the two groups when dividing into tensa retraction and sinus cholesteatoma subgroups. When comparing the types of tympanoplasty, the type II group reconstructed with cartilage palisades contained a higher number of ears with a normal compliance (0.2-1.6 mL) but a higher number of ears with a tympanometric width of more than 150 mmH2O. Regarding the number of ears with normal tympanometries, there was no significant difference between the palisade and the fascia group. The late functional hearing results were better in ears reconstructed with cartilage palisades, with functional success in 71%, compared with 54% in the group with fascia grafting. This difference in functional results was particularly pronounced in ears with an abnormal tympanogram (68% vs. 29%). Compared to fascia grafting, the present study showed better late functional hearing results after drum reconstruction using cartilage palisades, despite comparable tympanometric findings. Cartilage palisade reconstruction seems to provide better functional results, especially in ears with a poor tubal function, which is the common situation after cholesteatoma surgery.


Coupling the valley degree of freedom to antiferromagnetic order.
Conventional electronics are based invariably on the intrinsic degrees of freedom of an electron, namely its charge and spin. The exploration of novel electronic degrees of freedom has important implications in both basic quantum physics and advanced information technology. Valley, as a new electronic degree of freedom, has received considerable attention in recent years. In this paper, we develop the theory of spin and valley physics of an antiferromagnetic honeycomb lattice. We show that by coupling the valley degree of freedom to antiferromagnetic order, there is an emergent electronic degree of freedom characterized by the product of spin and valley indices, which leads to spin-valley-dependent optical selection rule and Berry curvature-induced topological quantum transport. These properties will enable optical polarization in the spin-valley space, and electrical detection/manipulation through the induced spin, valley, and charge fluxes. The domain walls of an antiferromagnetic honeycomb lattice harbors valley-protected edge states that support spin-dependent transport. Finally, we use first-principles calculations to show that the proposed optoelectronic properties may be realized in antiferromagnetic manganese chalcogenophosphates (MnPX3, X = S, Se) in monolayer form.


Flexible implant arthroplasty of the radiocarpal joint. Surgical technique and long-term study.
The wrist joint is frequently impaired in rheumatoid, post-traumatic, and degenerative arthritis. Stable radiocarpal motion, even limited, can improve functional hand adaptations, especially if the proximal or distal joints are disabled. A flexible silicone intramedullary stemmed hinged implant was developed in 1967 to be used as an adjunct to resection arthroplasty of the radiocarpal joint while at the same time maintaining the radiocarpal relation and allowing wrist motion in all planes. The surgical technique includes proper contracture release, bone preparation, extensor tendon repair and balancing, and dorsal and palmar capsuloligamentous repair to allow only 60 degrees of total passive flexion/extension and 10 degrees radial/ulnar deviation. This procedure can be combined with ulnar head capping. Metal bone liners (grommets) may be used to protect the radiocarpal implant from sharp bone edges. From January 1970 to April 1983, 181 wrist implant procedures had been performed in 139 patients, most of whom had rheumatoid arthritis. Stable, pain-free functional motion was obtained in the majority of cases. Roentgenograms showed the implants to be well tolerated by bone. Complications were infrequent. Because this procedure does not require cementing or significant bone resection, revision or arthrodesis procedures are facilitated.


Magnetic bead-based colorimetric immunoassay for aflatoxin B1 using gold nanoparticles.
A competitive colorimetric immunoassay for the detection of aflatoxin B1 (AFB) has been established using biofunctionalized magnetic beads (MBs) and gold nanoparticles (GNPs). Aflatoxin B1-bovine serum albumin conjugates (AFB-BSA) modified MBs were employed as capture probe, which could specifically bind with GNP-labeled anti-AFB antibodies through immunoreaction, while such specific binding was competitively inhibited by the addition of AFB. After magnetic separation, the supernatant solution containing unbound GNPs was directly tested by UV-Vis spectroscopy. The absorption intensity was directly proportional to the AFB concentration. The influence of GNP size, incubation time and pH was investigated in detail. After optimization, the developed method could detect AFB in a linear range from 20 to 800 ng/L, with the limit of detection at 12 ng/L. The recoveries for spiked maize samples ranged from 92.8% to 122.0%. The proposed immunoassay provides a promising approach for simple, rapid, specific and cost-effective detection of toxins in the field of food safety.


Rehabilitation of synovitis in patients with haemophilia.
Monitoring the synovium is a central requirement in haemophilia. In cases of acute synovitis, a sufficiently high dosage of coagulation factor should be used immediately, and pain control and anti-inflammatory treatment are essential. Severe effusion should be aspirated and persistent inflammation should be treated with steroid injections. In relation to physical therapy, cryotherapy with CO(2), and CP current after Bernhard should be used, if appropriate in combination with ultrasound and phonophoresis with Voltaren [Voltarol] Emulgel. Early functional treatment is essential following a short individually variable period of immobilization, with the aim of restoring flexibility, coordination and strength (closed chain). If the treatment is insufficient and chronic synovitis develops, consideration must be given after 2-3 month of early synovectomy, by chemical, radio-active, arthroscopic techniques, or by arthrotomy. The physical therapy following operations of this sort should be regarded as the same as for acute synovitis. The rehabilitation of synovitis is independent of co-infections.


DAX1 origin, function, and novel role.
The orphan nuclear receptor NR0B1 encodes the DAX1 protein, which stands for the dosage sensitive sex-reversal (DSS), adrenal hypoplasia congenita (AHC) critical region on the X-chromosome, gene 1. DAX1 was initially identified as part of a contiguous gene syndrome and is known to function in the proper formation of the adult adrenal gland. It has been hypothesized that DAX1 is responsible for the establishment and maintenance of the steroidogenic axis of development. Recent insight from the murine ortholog Dax1 along with reports of an alternatively spliced variant in humans suggests that Dax1 has additional functional roles beyond those previously understood. Here, we review DAX1/Dax1 known functional roles and the recently hypothesized function in the development of the embryo and in the maintenance of embryonic stem cell pluripotency.


Patient reported experiences and treatment outcomes of orthodontic patients treated within secondary care settings in the South West of England during the COVID-19 pandemic.
To assess the impact of the temporary cessation of orthodontic services on patients undergoing treatment during the COVID-19 pandemic. Two-phase multicentre service evaluation. Secondary care orthodontic departments in the South West of England. Phase 1 - Patient-Reported Experience Measure questionnaire (PREM). The questionnaire was distributed to patients who had undergone orthodontic treatment during the COVID-19 pandemic once services had resumed. Phase 2 - assessment of treatment outcomes, specifically with the Peer Assessment Rating (PAR) Index. A total of 280 PAR scores were obtained from a cohort of patients treated before and during the pandemic. A total of 711 PREM questionnaires were completed. Participants generally felt relaxed when visiting secondary care settings, orthodontic departments and whilst wearing orthodontic appliances during the pandemic. Nearly 40% of participants were concerned that the pandemic would impact on their treatment, particularly treatment length. Treatment outcomes revealed that patients treated before and during the pandemic experienced percentage PAR score reductions of 83.9% and 80.6%, respectively. Patients receiving treatment during the pandemic experienced longer treatment durations of 126 days. During the pandemic, low levels of anxiety were reported with respect to receiving orthodontic treatment in secondary care settings. Irrespective of the pandemic, a high standard of orthodontic treatment was provided. However, patient concerns regarding treatment length were justified.


Tooth auto-transplantation as an alternative treatment option: A literature review.
Rapidly evolving implantation and alveolar ridge reconstruction techniques created a new area in modern dentistry where tooth loss is no longer a problem. Endless variations of implant's length, diameter, surface, and design along with autogenous, alogenous, aloplastic, or xenogenous bone substitutes made it possible to recreate physiological occlusion, esthetic and masticatory function. However, none of nowadays technologies in implant dentistry have the potential to adapt to a growth and development changes of a child's jaw. Therefore, patient's young age is a restriction for implantation and a particular challenge for a dentist willing to restore missing tooth. Thus, tooth auto-transplantation can be a good choice for treatment. The objective of this review is to underline the biologic principles required for successful auto-transplantation of teeth. Limits, indications, technique, and prognosis will be analyzed.


Interdisciplinary approach and orthodontic options for treatment of advanced periodontal disease and malocclusion: a case report.
Patients with a compromised periodontal condition and a breakdown in occlusal support may require periodontal and prosthodontic treatment in conjunction with orthodontic treatment. Orthodontic treatment of these patients is possible and would involve removal of inflammation and occlusal interference and provision of an environment for proper restorative rehabilitation. A different approach to the orthodontic treatment of these patients is required in terms of treatment manner, stabilizing anchorage systems, force systems, retention, and plaque control during treatment. This report describes the case of a 49-year-old woman with severely compromised periodontal tissues, multiple missing teeth, and malocclusion. Highly esthetic and functional results were achieved by treatment with orthodontics as well as periodontal therapy, including guided tissue regeneration and implant restoration with sinus lift.


Nurses in research: the treatment of acne.
Many nurses undertake research, either as part of a research team or independently as the research lead. Nurses are well placed to participate in research, using their clinical skills to the benefit of both the participants and the research objectives. This article focuses on the value of nurses in research. Using the example of their own experiences of a large NHS clinical trial, the authors demonstrate how nurses can become involved in research, what skills are needed, and how nursing skills and experience can contribute to the role of a clinical assessor/research nurse.


General pharmacological properties of the potent angiotensin converting enzyme inhibitor rentiapril.
Pharmacological properties of (2R,4R)-2-(o-hydroxyphenyl)-3-(3-mercaptopropionyl)-4- thiazolidinecarboxylic acid (rentiapril, SA 446), a potent inhibitor of angiotensin converting enzyme, were examined. SA 446 given intravenously lowered blood pressure in anesthetized rats and rabbits dose-dependently, while it had no remarkable effect in conscious rats even at a dose of 100 mg/kg orally or intravenously. SA 446 had no effect on heart rate in anesthetized rabbits up to 100 mg/kg i.v. In anesthetized dogs, SA 446 at a dose of 1 mg/kg i.v. produced decrease in blood pressure accompanied with coronary and vertebral arterial vasodilations, but gave no change in heart rate. SA 446 had no influence on respiration of anesthetized rabbits at doses up to 100 mg/kg i.v. The drug showed no effect on contractile force or beating rate of isolated guinea pig atria at concentrations up to 10(-4) mol/l, but caused vasoconstriction of isolated rabbit ear vessels at a 0.1 ml dose of 3 X 10(-2) mol/l solution or more and relaxation of isolated rat thoracic aortas at concentrations over 3 X 10(-4) mol/l. SA 446 had no influence on beta 1- or beta 2-adrenoceptors of isolated guinea pig atria and tracheas, respectively. Neither was a calcium antagonistic action observed. SA 446 did not influence the central nervous system, neuromuscular transmission, spontaneous movement or contractile response to several agonists of isolated smooth muscles, secretion of digestive glands, blood coagulation, hemolysis or blood glucose level, and it showed no muscle relaxant, antispasmodic or local anesthetic effect.(ABSTRACT TRUNCATED AT 250 WORDS)


Calophyline A, a new rearranged monoterpenoid indole alkaloid from Winchia calophylla.
Calophyline A (1), a novel unprecedented rearranged monoterpenoid indole alkaloid, along with a new natural product N-methyl aspidodasycarpine (2) and six known analogues, was isolated from the trunk barks of Winchia calophylla. The structure of compound 1 was elucidated on the basis of spectroscopic data and then confirmed by a single-crystal X-ray crystallographic analysis. A hypothetical biogenetic pathway for compound 1 was proposed. All isolated compounds were evaluated for their in vitro cytotoxicity against a small panel of human cancer cell lines.


How accurate are the suggested diagnoses on biopsy requisitions for inflammatory skin disease? A retrospective study of 348 cases.
Clinical information is often critical to the histopathologic interpretation of cutaneous biopsies for inflammatory skin diseases. This information is often conveyed to the dermatopathologist as list of possible diagnoses. We reviewed 348 cases of biopsied inflammatory skin disease and measured the correlation between the original clinical differential diagnoses on the pathology requisition and the patient's final diagnosis. The final diagnosis was included among the suggested diagnoses in 270 of 348 (78%) cases reviewed. In 191 of 270 (71%) correctly diagnosed cases, the final diagnosis was listed first among those included in the differential diagnoses. The total number of suggested diagnoses did not correlate with overall diagnostic accuracy. The most commonly neglected diagnoses were eczematous dermatitis, psoriasis, lichen planus, and granuloma annulare. We conclude that the differential diagnosis submitted with pathology specimens for inflammatory skin disease includes the final diagnosis in a majority of cases. The first listed diagnosis has the highest positive predictive value. Submitting longer differential diagnosis lists did not improve diagnostic accuracy.


Gross osteology and radiology of the pelvic limb of the adult small East African goat.
The aim of this study was to provide the detailed normal gross osteology and radiographic anatomy of the pelvic limb in adult small East African goats as a reference for clinical use, biomedical research and teaching. Radiography of the pelvic limb was performed in five adult small East African goats. Bone specimens of four skeletally mature small East African goats were used for gross osteological study. The ilial wing was wide. The ischiatic tuberosity was prominent and well developed. The acetabulum was rounded. The minor trochanter was located caudomedially, and the femoral trochlea was deep and narrow. The lateral and medial condyles of the femur were approximately of the same size. The tibial tuberosity was prominent, and the cochlea grooves were deep with a pronounced intermediate ridge. The trochlea of the talus was deep. The patella presented a prominent tuberosity on the cranial surface. The metatarsal sesamoid bone was seen in all animals. The observed gross osteology and radiographic anatomy of the pelvic limb of small East African goats was consistent with the presence of strong extensor muscles of the hip, stifle and tarsus for propulsion during terrestrial walking and trotting.


P013 Resolution of Infliximab Associated Infusion Hypersensitivity After Switching to Biosimilar Infliximab-dyyb.
Background: Administration of infliximab for the treatment of inflammatory bowel disease has a well-recognized risk of infusion-related (IR) adverse events. The recent introduction of the biosimilar infliximab-dyyb (Inflectra®) has been shown to have similar efficacy with comparable safety profile when compared to infliximab; however, although the active ingredients are similar, the inactive ingredients are different. We present a case of a 26-year-old female with ulcerative colitis who had resolution of her IR hypersensitivity when switched from infliximab to infliximab-dyyb. A 26-year-old female with a past medical history of ulcerative pancolitis presented to our clinic with the chief complaint of rash associated with her infliximab infusions. She described pruritic raised lesions which would occur on her upper and lower extremities during her infusions. She denied any shortness of breath or wheezing, and her symptoms were well controlled with methylprednisolone 40mg IV prior to her infusions. Previously, she had been treated for her UC with oral mesalamine, azathioprine and intermittent prednisone and did not have any adverse reactions to these medications. She has no known allergies to other medications and her peripheral eosinophil count was 1.6%. She was initially started on infliximab 5mg/kg every 8 weeks since 2013 and had achieved clinical as well as endoscopic remission with her most recent colonoscopy graded as Mayo 0. On account of her infusion reaction, drug antibodies were checked but were not detected. Infliximab level was 8.8 μg/ml. Due to insurance she was required to switch to infliximab-dyyb. After switching to the biosimilar, she has not had any infusion related reactions and no longer requires premedication with methylprednisolone with her infusions. Immediate IR reactions have been reported in 5-23% of IBD patients receiving infliximab and those who develop antibodies towards infliximab have a 2-fold risk of acute IR events. Side effects have been reported to be the primary reason for discontinuation of infliximab, and studies have shown that discontinuation can lead to an increased risk of relapse of inflammatory bowel disease. Although infliximab and infliximab-dyyb have analogous active ingredients, the inactive ingredients differ. Specifically, infliximab-dyyb lacks monobasic sodium phosphate and dibasic sodium phosphate, which acts as an emulsifier which we believe contributed to her IR with originator biologic infliximab. It is important to recognize these differences as IR hypersensitivities may be attributed to inactive ingredients; especially when antibodies are negative. Our case report suggests that a switch to biosimilar infliximab in patients may provide added benefit especially in those that have reactions occurring from inactive ingredients in the originator biologic.


Intensive studies of patients and the experiences of investigators and clinicians.
Mental processes, normal or abnormal, are complex and multifaceted, needing to be viewed from diverse perspectives. But our field has split increasingly into two discrete groups. One group includes those investigators and clinicians who are often seen as most scientific and have restricted themselves more and more exclusively to directly observable, generally superficial phenomena and patients as classified according to those phenomena. Such variables can be reliably rated, a crucial aspect of any scientific endeavor. But in this group there has been a tendency to be like the person who lost the keys in the middle of the block but looked for them at the corner because "the light is better here." Those of us in this group have tended to act as though, if we can't measure a phenomenon with relative ease, it doesn't exist--potentially the antithesis of an adequate science. Others, and they have become rarer, have focused on understanding the psychological processes of individuals with mental disorder in great depth, while paying less attention to questions of scientific approaches to proof.


[Analgesics; the use of aspirin in dogs; effects of tablet type and food intake on plasma salicylate level].
Administration of acetylsalicylic acid (aspirin) in the dog may cause gastric mucosal damage. Enteric-coated tablets protect the canine stomach during oral aspirin medication. A therapeutic plasma salicylate concentration can be attained using enteric-coated aspirin tablets at a dosage of 25 mg/kg TID. In a series 4 of experiments using adult beagle and large mixed breed dogs and two types enteric-coated tablets, the influence of food intake on the plasma salicylate concentration was studied. Tablets were administered with 8h intervals and food intake was either once daily or three time daily with 8h intervals. Plasma salicylate concentrations were also studied during fasting. It is concluded that, when using enteric-coated tablets, the plasma salicylate concentration in the dog after oral medication is strongly influenced by the aspirin dosage, the tablet type and the feeding pattern. Large enteric-coated tablets may accumulate in the stomach over several days and are not suitable for use in the dog. The gastric accumulation is caused by the enteric-coating of the large tablets and not by the aspirin medication.


An 11-bp deletion in the arylsulfatase A gene of a patient with late infantile metachromatic leukodystrophy.
Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. Examination of the arylsulfatase A gene in a patient suffering from late infantile metachromatic leukodystrophy revealed an 11-bp deletion in exon 8. Although this allele produces normal amounts of ASA mRNA, no arylsulfatase A cross-reacting material could be detected in cultured fibroblasts from the patient. The patient was found to be a compound heterozygote, the other allele is also known to generate no ASA polypeptides. This patient is another example where absence of ASA polypeptides correlates with the severe late infantile form of metachromatic leukodystrophy.


Dilation of esophageal strictures. A new technique controlled by fiberoptic endoscopy.
Dilation of peptic esophageal strictures visually controlled by means of fiberoptic endoscopy was carried out in 16 patients. The dilation was performed by passing the woven silk bougies alongside the endoscope, so that the process could be observed in detail. The technique affords a better view of the procedure because of a wider visual angle and because the field of vision is not blocked by the bougie, as would be the case with the rigid endoscope. The size of the bougie employed is not limited by the size of the endoscope. All 16 patients, with and without subsequently undergoing Nissen fundoplication, were able to eat a normal diet after therapy.


Increasing carbon, nutrient and trace metal accumulation driven by development in a mangrove estuary in south Asia.
Mangrove forests sequester organic carbon, nutrients and toxic metals sorbed to fine sediment, and thus restrict the mobility of pollutants through estuarine environments. However, mangrove removal and environmental degradation caused by industrial activity and urban growth can impact the ability of mangrove communities to provide these critical ecosystem services. Here, we use sediment profiles from an impacted tropical estuary in southwest India to provide a c. 70-year record of carbon, nutrient and trace metal burial in the context of rapid urban development and the systemic removal of mangrove communities. Our results show that carbon and nutrient accumulation rates increase sharply during the 1990's in accordance with the high rates of deforestation. Nitrogen and phosphorus accumulation rates increased fourfold and twofold, respectively, during the same period. Organic carbon accumulation was fivefold higher than the global average during this period, reflecting intense deforestation during the last three decades. The enrichment of Hg, Zn, Pb, Mo, Ni, Cu and Mn demonstrate clear anthropogenic impact starting in the 1950's and peaking in 1990. Mercury, the trace metal with the highest enrichment factor, increased sevenfold in the most recent sediments due to increased fossil fuel emissions, untreated water and incineration of medical waste and/or fertilizers used in aquaculture. Organic carbon isotope (δ13C) and C:N molar ratios indicate shifts to more terrestrial-derived source of organic matter in the most recent sediments reflecting growing deforestation of which may be prevalent in southeast Asia due to increasing development. This study emphasizes the critical role played by mangrove ecosystems in attenuating anthropogenically-derived pollutants, including carbon sequestration, and reveals the long-term consequences of mangrove deforestation in the context of rapidly developing economies.


Blockade of DNA methylation enhances the therapeutic effect of gefitinib in non-small cell lung cancer cells.
The sensitivity of lung cancer to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has been found to be associated with mutations in the tyrosine kinase domain of EGFR. However, not all mutations are sensitive to gefitinib. While CpG island methylation in the promoter region of the EGFR gene and transcriptional silencing are common in solid tumors, the role of the EGFR gene promoter methylation in affecting resistance to TKIs in non-small cell lung cancer (NSCLC) remains unknown. In this study, we examined the correlation between EGFR gene promoter methylation and the therapeutic effect of gefitinib in NSCLC cells. Three NSCLC cell lines with different EGFR mutation statuses and levels of sensitivity to EGFR-TKIs were used in this study: H1650 (del E746-A750), H1299 (wild-type EGFR) and PC-9 (del E746-A750). Cells were treated with gefitinib or 5-aza-2'-deoxy cytidine (5-aza-CdR), a methylation inhibitor, alone or in combination. Subsequently, the methylation status of the EGFR gene promoter was examined by methylation-specific PCR (MSP). Cell survival and apoptosis assays were performed using the Cell Counting Kit-8 (CCK-8) and flow cytometry. In addition, western blot analysis and quantitative real-time PCR were used to examine the expression levels of EGFR protein and mRNA. Our study showed that the promoter region of the EGFR gene in PC-9 cells was unmethylated, and that the cells were sensitive to gefitinib. By contrast, the promoter region of the EGFR gene in the H1650 and H1299 cells was methylated, and the cells were resistant to gefitinib. Of note, the combination treatment with 5-aza-CdR and gefitinib further enhanced the growth inhibitory effects and led to the induction of apoptosis, while a significant reduction in the expression of EGFR protein and mRNA was observed in the H1650 and H1299 cells. These results suggest that blockade of DNA methylation may enhance the antitumor effects of EGFR-TKIs and gefitinib in NSCLC cells. Thus, EGFR gene promoter methylation may be a potential mechanism for acquired resistance to gefitinib.


Effects of Diode Laser, Gaseous Ozone, and Medical Dressings on Enterococcus faecalis Biofilms in the Root Canal Ex Vivo.
The objective was to compare the antibacterial effects of adjunctive disinfection using diode laser and gaseous ozone compared to the medical dressings calcium hydroxide (Ca(OH)2) and chlorhexidine gel (CHX-Gel) on Enterococcus faecalis biofilms in human root canals ex vivo. Root canals of 180 human extracted teeth were infected by E. faecalis and divided into 3 main groups (G): G1, control; G2, instrumentation and irrigation using 0.9% NaCl; G3, instrumentation and irrigation using 1% NaOCl. In each main group, the following treatments were applied: gaseous ozone, diode laser, and medical dressings of Ca(OH)2 or CHX-Gel for 7 days (n = 15). Reduction of colony forming units (CFUs) inside the root canal of planktons and frequencies of adherent bacteria after treatment were calculated. Bacterial reduction was significantly affected by the irrigation protocol (p < 0.0005) and the disinfection method (p < 0.0005), and a significant interaction between both factors could be observed (p < 0.0005; ANOVA). In G3 (instrumentation using 1% NaOCl), no significant effect of disinfection methods could be demonstrated on planktonic bacteria (p = 0.062; ANOVA) and frequencies of adherent bacteria (p > 0.05; chi-square test). Instrumentation and irrigation using NaOCl combined with ozone or laser application resulted in comparable bacterial reduction on E. faecalis to the application of medical dressings.


COVID-19 vaccination in pregnancy: early experience from a single institution.
Pregnant women are at increased risk for morbidity owing to infection with the COVID-19 virus.1 Vaccination presents an important strategy to mitigate illness in this population. However, there is a paucity of data on vaccination safety and pregnancy outcomes because pregnant women were excluded from the initial phase III clinical trials. Our objective was to describe the maternal, neonatal, and obstetrical outcomes of women who received a messenger RNA (mRNA) COVID-19 vaccination while pregnant during the first 4 months of vaccine availability. This was an institutional review board-approved descriptive study of pregnant women at New York University Langone Health who received at least 1 dose of an mRNA COVID-19 vaccination approved by the US Food and Drug Administration (FDA) (Pfizer-BioNTech or Moderna) from the time of the FDA Emergency Use Authorization to April 22, 2021. Eligible women were identified via search of the electronic medical record (EMR) system. Vaccine administration was ascertained via immunization records from the New York State Department of Health. Women were excluded if they were vaccinated before conception or during the postpartum period. Charts were reviewed for maternal demographics and pregnancy outcomes. Descriptive analyses were performed using the R software version 4.0.2 (The R Foundation, Boston, MA). We identified 424 pregnant women who received an mRNA vaccination. Of those, 348 (82.1%) received both doses and 76 (17.9%) received only 1 dose. The maternal characteristics and vaccination information are shown in Table 1. Of the included women, 4.9% had a history of a confirmed COVID-19 diagnosis before vaccination. After vaccination, no patient in our cohort was diagnosed with COVID-19. In terms of the pregnancy outcomes, 9 women had spontaneous abortions, 3 terminated their pregnancies, and 327 have ongoing pregnancies. Of the women included, 85 delivered liveborn infants. There were no stillbirths in our population. Of the 9 spontaneous abortions, 8 occurred during the first trimester at a range of 6 to 13 weeks' gestation. There was 1 second trimester loss. The rate of spontaneous abortion among women vaccinated in the first trimester was 6.5%. The 327 women with ongoing pregnancies have been followed for a median of 4.6 weeks (range, 0-17 weeks) following their most recent dose. A total of 113 (34.6%) women, initiated vaccination during the first trimester, 178 (54.4%) initiated vaccination during the second trimester, and 36 (11.0%) during the third trimester. Following the vaccination, 2 fetuses (0.6%) developed intrauterine growth restriction, whereas 5 (1.5%) were diagnosed with anomalies. Outcomes for the 85 women who delivered are shown in Table 2. Of the women who delivered, 18.8% were diagnosed with a hypertensive disorder of pregnancy. The rate of preterm birth was 5.9%. One preterm delivery was medically indicated, whereas the remaining 3 were spontaneous. A total of 15.3% of neonates required admission to the neonatal intensive care unit (NICU). Of the NICU admissions, 61.5% were because of hypoglycemia or an evaluation for sepsis. Other reasons for admission included prematurity, hypothermia, and transient tachypnea of the newborn. Of all the neonates, 12.2% were small for gestational age (SGA) per the World Health Organization standards. This series describes our experience with women who received an mRNA COVID-19 vaccine during pregnancy. In line with other published findings,2 we observed no concerning trends. There were no stillbirths. Our 6.5% rate of spontaneous abortion is within the expected rate of 10%,3 and our preterm birth rate of 5.9% is below the national average of 9.5%.4 Our rate of pregnancy-related hypertensive disorders is higher than our baseline institutional rate of 9.5%, however, this may be because of the underlying characteristics of our study population or skewing of our small sample size. Our 12.2% rate of SGA neonates is near the expected value based on the definition that 10% of neonates will be SGA at birth. The NICU admission rate is at par with our institutional rate of 12%. To date, most women in this series have had uncomplicated pregnancies and have delivered at-term. Strengths of this study include using the EMR system to identify subjects and gather data. We did not rely on self-enrollment and self-report, thereby reducing selection and recall bias. By performing manual chart reviews, we obtained detailed and reliable information about individual patients. One limitation of this study is the lack of a matched control group consisting of unvaccinated pregnant women and therefore direct conclusions could not be drawn about the relative risks of complications. In addition, our cohort is small and may not be generalizable. Finally, many women included are healthcare workers who had early access to vaccinations. As more pregnant women become eligible for the COVID-19 vaccinations, there is an urgent need to report on the maternal, neonatal, and obstetrical outcomes of COVID-19 vaccinations during pregnancy. The results of this study can be used to counsel and reassure pregnant patients facing this decision.


The use of MR imaging in treatment planning for patients with rectal carcinoma: have you checked the "DISTANCE"?
Rectal cancer is a common and serious disease in the Western hemisphere. Optimal treatment of rectal cancer involves a multidisciplinary approach, with collaboration required between radiologists, oncologists, surgeons, and pathologists to achieve local control and decrease the rate of recurrence. Several studies have been published that show the ability to accurately stage rectal cancer with magnetic resonance (MR) imaging. Moreover, advances in preoperative therapies require accurate preoperative staging with MR imaging to select those patients who may benefit from more intensive treatment, without subjecting those who will not benefit to unnecessary treatment. As we enter an era of individualized patient care, stratified according to the risk of both local and distant failure, imaging takes on the same importance as the tumor type and genetic susceptibility. MR imaging is now an essential tool to enable the oncology team to make appropriate treatment decisions. However, rectal cancer evaluation with MR imaging remains a challenge in the hands of nonexperts. This article describes a mnemonic device, "DISTANCE," to enable a systematic approach to the interpretation of MR images, thereby enabling all the clinically relevant features to be adequately assessed: DIS, for Distance from the Inferior part of the tumor to the transitional Skin; T, for T staging; A, for Anal complex; N, for Nodal staging; C, for Circumferential resection margin; and E, for Extramural vascular invasion.


Atypical neural topographies underpin dysfunctional pattern separation in temporal lobe epilepsy.
Episodic memory is the ability to remember events from our past accurately. The process of pattern separation is hypothesized to underpin this ability and is defined as the capacity to orthogonalize memory traces, to maximize the features that make them unique. Contemporary cognitive neuroscience suggests that pattern separation entails complex interactions between the hippocampus and neocortex, where specific hippocampal subregions shape neural reinstatement in the neocortex. To test this hypothesis, the current work studied both healthy controls and patients with temporal lobe epilepsy who presented with hippocampal structural anomalies. We measured neural activity in all participants using functional MRI while they retrieved memorized items or lure items, which shared features with the target. Behaviourally, patients with temporal lobe epilepsy were less able to exclude lures than controls and showed a reduction in pattern separation. To assess the hypothesized relationship between neural patterns in the hippocampus and neocortex, we identified the topographic gradients of intrinsic connectivity along neocortical and hippocampal subfield surfaces and determined the topographic profile of the neural activity accompanying pattern separation. In healthy controls, pattern separation followed a graded topography of neural activity, both along the hippocampal long axis (and peaked in anterior segments that are more heavily engaged in transmodal processing) and along the neocortical hierarchy running from unimodal to transmodal regions (peaking in transmodal default mode regions). In patients with temporal lobe epilepsy, however, this concordance between task-based functional activations and topographic gradients was markedly reduced. Furthermore, person-specific measures of concordance between task-related activity and connectivity gradients in patients and controls were related to inter-individual differences in behavioural measures of pattern separation and episodic memory, highlighting the functional relevance of the observed topographic motifs. Our work is consistent with an emerging understanding that successful discrimination between memories with similar features entails a shift in the locus of neural activity away from sensory systems, a pattern that is mirrored along the hippocampal long axis and with respect to neocortical hierarchies. More broadly, our study establishes topographic profiling using intrinsic connectivity gradients, capturing the functional underpinnings of episodic memory processes in a manner that is sensitive to their reorganization in pathology.


An illustrated guide for characters and terminology used in descriptions of Phlebotominae (Diptera, Psychodidae).
Phlebotomine (Diptera, Psychodidae, Phlebotominae) taxonomy has been studied extensively, primarily due to the role of these flies as vectors of various parasites, including species of Leishmania, Bartonella and arboviruses that cause diseases in humans and other vertebrates. We present some topics discussed at a round-table on phlebotomine taxonomy held at the Ninth International Symposium on Phlebotomine Sandflies (ISOPS IX) in Reims, France, in June 2016. To date, approximately one thousand phlebotomine species have been described worldwide, although in varying languages and mostly without standardization of characters and terminology. In the interest of standardization, we list the characters that should minimally be considered in the description of new phlebotomine taxa as well as annotated illustrations of several characters. For these characters, multiple illustrations are provided to show some of the variations. The preferred terms for all pertinent characters are listed as well as their synonyms in English, Portuguese, and French. Finally, we offer an updated list of abbreviations to be used for generic and subgeneric names.


Organelle interactions and possible degradation pathways visualized in high-pressure frozen algal cells.
Summary Organelle interactions, although essential for both anabolic and catabolic pathways in plant cells have not been examined in detail so far. In the present study the structure of different organelle-organelle, organelle-vesicle and organelle-membrane interactions were investigated in growing and nongrowing cells of the green alga Micrasterias denticulata by use of high pressure freeze fixation and energy filtering transmission electron microscopy. It became clear that contacts between mitochondria always occur by formation of a cone-shaped protuberance of one of the mitochondria which penetrates into its fusion partner. In the same way, structural interactions between mitochondria and mucilage vesicles and between microbodies and mucilage vesicles are achieved. Lytic compartments contact mitochondria or mucilage vesicles again by forming protuberances and by extending their contents into the respective compartment. Detached portions of mitochondria are found inside lytic compartments as a consequence of such interactions. Mitochondria found in contact with the plasma membrane reveal structural disintegration. Our study shows that interactions of organelles and vesicles are frequent events in Micrasterias cells of different ages. The interactive contacts between lytic compartments and organelles or vesicles suggest a degradation pathway different from autophagy processes described in the literature. Both the interactions between vesicles and organelles and the degradation pathways occur independently from cytoskeleton function as demonstrated by use of cytochalasin D and the microtubule inhibitor amiprophos-methyl.


Comparison of genomic, plasmid, synthetic, and combined DNA probes for detecting Plasmodium falciparum DNA.
Total genomic Plasmodium falciparum DNA, the plasmid clone pRepHind, and a 21-base-long synthetic DNA probe (PFR1), the sequence of which was derived from pRepHind, were hybridized with DNA from various species of the phylum Apicomplexa. The genomic probe hybridized with P. reichenowi and P. falciparum DNA and significantly cross-hybridized with DNA of all the other Plasmodium species tested. The synthetic and plasmid probes hybridized to P. falciparum DNA and at reduced levels to P. reichenowi but did not hybridize to P. vivax, P. malariae, P. ovale, P. fragile, P. inui, P. knowlesi, Babesia bovis, B. microti, B. bigemina, Anopheles sp., Pan sp., Aotus sp., or human DNA. Southern blot analysis indicated that approximately 60 distinct restriction enzyme fragments from P. falciparum DNA were similarly detected by PFR1 and pRepHind. A method was developed by using a second brief hybridization with synthetic DNA to amplify signals from samples that were previously hybridized with plasmid-borne repetitive DNA. This amplification procedure was shown to allow the detection of 0.005% P. falciparum parasitemias from 10-microliter samples of blood from patients in Kenya.


Pathways for orofacial pain sensation in the trigeminal brain-stem nuclear complex of the Macaque monkey.
Eleven Macaque monkeys underwent a variety of lesions in the trigeminal afferent system; namely, tractotomy, rhizotomy, and radiofrequency destruction of various components of the bulbospinal trigeminal nuclear complex. Behavioral responses were evaluated before and after the lesions using a quantitative paradigm which measured lever-pressing in response to electrical stimulation of the dental pulp or facial skin, and by assessing adversive responses to facial cutaneous and intraoral pin-scratch. Thresholds for lever-pressing in response to cutaneous facial stimulation were elevated by tractotomy, elevated further by a combination of tractotomy and rhizotomy of the seventh, ninth, and 10th cranial nerves and cervical dorsal roots C1-3, and maximally elevated by complete radiofrequency destruction of the trigeminal nucleus caudalis. These lesions also abolished adversive responses to cutaneous facial pin-scratch. None of these lesion combinations, however, altered lever-pressing responses to dental pulp stimulation. Radiofrequency destruction of the trigeminal nuclei principalis, oralis, and interpolaris caused elevations of lever-pressing thresholds in response to dental pulp stimulation, and also smaller but statistically significant elevations on cutaneous electrical stimulation. Mild reductions in adversive responses to cutaneous pin-scratch were also produced by these rostral nuclear lesions, suggesting analgesia. The experiments suggest that primary afferent fibers for dental pain perception travel only in the trigeminal nerve and that these fibers relay via the trigeminal brain-stem nuclei principalis, oralis, and interpolaris. Primary afferent fibers for cutaneous facial pain perception travel in the trigeminal, facial, glossopharyngeal, and vagus nerves, and the upper cervical dorsal and ventral roots, and these afferents relay mainly in the trigeminal nucleus caudalis.


The Chilean wild raspberry (Rubus geoides Sm.) increases intracellular GSH content and protects against H2O2 and methylglyoxal-induced damage in AGS cells.
The Chilean raspberry Rubus geoides Sm. (Rosaceae) is a native species occurring in the Patagonia. Five R. geoides samples were assessed for phenolic content and composition, antioxidant activity, effect on total reduced glutathione (GSH) synthesis and protective effect against H2O2 and methylglyoxal (MGO)-induced stress in epithelial gastric AGS cells. The HPLC-DAD/ESI-MS profiles allowed the tentative identification of 39 phenolics including flavonol glycosides and tannins. R. geoides presented higher total phenolic and flavonoid content than Rubus idaeus. Two out of the five phenolic enriched R. geoides extracts (PEEs) exhibited better antioxidant activity than R. idaeus in the DPPH, FRAP and TEAC assays. A significant cytoprotective activity was observed when AGS cells were pre-incubated with extracts and subsequently challenged with H2O2 or MGO. Treatment with the PEEs increased the intracellular GSH content. R. geoides fruit extracts may induce the activation of intracellular protection mechanisms against oxidative and dicarbonyl-induced stress.


Epilepsy: case report and analysis of clinical management problems.
Epilepsy is a major cause of morbidity and accounted for up to 40% of psychiatric outpatient attendances in the experience of the author in Transkei, South Africa. In many cases clinical diagnosis and management were easy. In this paper, the author analyses the clinical management problems presented by seven patients between January 1986 and May 1989. A detailed case report is presented to illustrate difficulties in management. It is suggested that ethosuximide might be effective in the control of probable partial seizure disorders. Underlying electrophysiological considerations are discussed. It is noted, however, that it may not be easy to differentiate between partial or generalised seizure disorders on clinical grounds.


Regret about the decision to start dialysis: a cross-sectional Dutch national survey.
More older patients with end-stage renal disease (ESRD) are starting dialysis. Elderly patients often prefer treatments that focus on quality of life rather than primarily extending life and a substantial group of elderly dialysis patients might regret their decision to start dialysis. Healthcare provider and patient-related factors may be involved. Our objective was to measure the percentage of patients in the Netherlands who regretted their decision to start dialysis. Cross-sectional Dutch national survey of dialysis patients. A short questionnaire about age, satisfaction with pre-dialysis education, present treatment, dialysis initiation, regret about decision to start dialysis and key figures in decision-making was developed. A total of 1371 questionnaires were returned for analysis from 28 dialysis units. Of the patients 7.4% regretted their decision to start dialysis, 50.5% reported the nephrologist's opinion to be crucial in decision-making and these patients experienced more regret than those who made the decision themselves (odds ratio, OR: 1.81). When family influenced decision-making more regret was experienced compared with those who decided themselves (OR: 2.73). Older age was associated with less regret (p = 0.02) and higher treatment satisfaction (p < 0.001); 52.8% of participants described dialysis initiation as being sudden. The majority of patients did not regret their decision to start dialysis. Older patients were more satisfied with their treatment and felt less regret. The nephrologist's and the family's opinion were directional in decision-making on ESRD treatment options and were associated with more regret, especially in younger patients.


Systolic-diastolic hypertension versus isolated systolic hypertension and incident heart failure in older adults: Insights from the Cardiovascular Health Study.
Isolated systolic hypertension (ISH) is common in older adults and is a risk factor for incident heart failure (HF). We examined the association of systolic-diastolic hypertension (SDH) with incident HF and other outcomes in older adults. In the Cardiovascular Health Study (CHS), 5776 community-dwelling adults≥65years had data on baseline systolic and diastolic blood pressure (SBP and DBP). We excluded those with DBP<60mmHg (n=821), DBP≥90 and SBP<140mmHg (n=28), normal BP, taking anti-hypertensive drugs (n=1138), normal BP, not taking anti-hypertensive drugs, history of hypertension (n=193), and baseline HF (n=101). Of the remaining 3495, 1838 had ISH (SBP≥140 and DBP<90mmHg) and 240 had SDH (SBP≥140 and DBP≥90mmHg). The main outcome was centrally-adjudicated incident HF over 13years of follow-up. Participants had a mean (±SD) age of 73 (±6)years, 57% were women, and 16% African American. Incident HF occurred in 25%, 22% and 11% of participants with ISH, SDH and no hypertension, respectively. Compared to no hypertension, multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident HF associated with ISH and SDH were 1.86 (1.51-2.30) and 1.73 (1.23-2.42), respectively. Cardiovascular mortality occurred in 22%, 24% and 9% of those with ISH, SDH and no hypertension, respectively with respective multivariable-adjusted HRs (95% CIs) of 1.88 (1.49-2.37) and 2.30 (1.64-3.24). Among older adults with hypertension, both SDH and ISH have similar associations with incident HF and cardiovascular mortality.


Artificial Intelligence's Use in the Diagnosis of Mouth Ulcers: A Systematic Review.
Artificial intelligence (AI) has been cited as being helpful in the diagnosis of diseases, the prediction of prognoses, and the development of patient-specific therapeutic strategies. AI can help dentists, in particular, when they need to make important judgments quickly. It can eliminate human mistakes in making decisions, resulting in superior and consistent medical treatment while lowering the workload on dentists. The existing studies relevant to the study and application of AI in the diagnosis of various forms of mouth ulcers are reviewed in this work. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed in the preparation of the review. There were no rule violations, with the significant exception of the use of a better search method that led to more accurate findings. Using search terms mainly such as AI, oral health, oral ulcers, oral herpes simplex, oral lichen planus, pemphigus vulgaris, recurrent aphthous ulcer (RAU), oral cancer, premalignant and malignant disorders, etc., a comprehensive search was carried out in the reliable sources of literature, namely PubMed, Scopus, Embase, Web of Science, Ovid, Global Health, and PsycINFO. For all papers, exhaustive searches were done using inclusion criteria as well as exclusion criteria between June 28, 2018, and June 28, 2023. An AI framework for the automatic categorization of oral ulcers from oral clinical photographs was developed by the authors, and it performed satisfactorily. The newly designed AI model works better than the current convolutional neural network image categorization techniques and shows a fair level of precision in the classification of oral ulcers. However, despite being useful for identifying oral ulcers, the suggested technique needs a broader set of data for validation and training purposes before being used in clinical settings. Automated OCSCC identification using a deep learning-based technique is a quick, harmless, affordable, and practical approach to evaluating the effectiveness of cancer treatment. The categorization and identification of RAU lesions through the use of non-intrusive oral pictures using the previously developed ResNet50 and YOLOV algorithms demonstrated better accuracy as well as adequate potential for the future, which could be helpful in clinical practice. Moreover, the most reliable projections for the likelihood of the presence or absence of RAU were made by the optimized neural network. The authors also discovered variables associated with RAU that might be used as input information to build artificial neural networks that anticipate RAU.


Neuritogenic activity of trichostatin A in adult rat retinal ganglion cells through acetylation of histone H3 lysine 9 and RARβ induction.
Like other CNS neurons, mature retinal ganglion cells (RGCs) cannot regenerate their axons after nerve injury due to loss of regenerative capacity. One of the reasons why they lose their capacity seems to be a dramatic shift in gene expression of RGCs under epigenetic modulation. In here, we found that levels of histone H3 lysine 9 acetylation decreased after birth in RGCs. This decrease showed good correlation with restriction of retinoic acid receptor β (RARβ) expression in RGCs after birth. Furthermore, we demonstrated that a histone deacetylase inhibitor, trichostatin A, induced axonal regeneration of adult rat RGCs through RARβ induction.


Visible absorption spectra of metal-catecholate and metal-tironate complexes.
Interactions between metals and catechol (1,2-dihydroxybenzene) or other ortho-dihydroxy moieties are being found in an increasing number of biological systems with functions ranging from metal ion internalization to biomaterial synthesis. Although metal-catecholate interactions have been studied in the past, we present the first systematic study of an array of these compounds, all prepared under identical conditions. We report the ultraviolet-visible absorption (UV-vis) spectra for catecholate and tironate complexes of the first row transition elements. Generation and identification of these species were accomplished by preparing aqueous solutions with varied ligand:metal ratios and subsequently titrating with base (NaOH). Controlled ligand deprotonation and metal binding resulted in sequential formation of complexes with one, two, and sometimes three catecholate or tironate ligands bound to a metal ion. We prepared the mono-, bis- and tris-catecholates and -tironates of Fe(3+), V(3+), V(4+)and Mn(3+), the mono- and bis-catecholates and -tironates of Cu(2+), Co(2+), Ni(2+), Zn(2+), Cr(2+) and Mn(2+), and several Ti(4+) and Cr(3+) species. The UV-vis spectra of each complex are described, some of which have not been reported previously. These data can now be applied to characterization of biological metal-catecholate systems.


Cross Calibration of the GE Prodigy and iDXA for the Measurement of Total and Regional Body Composition in Adults.
Dual-energy X-ray absorptiometry (DXA) body composition measurements are widely performed in both clinical and research settings, and enable the rapid and noninvasive estimation of total and regional fat and lean mass tissues. DXA upgrading can occur during longitudinal monitoring or study; therefore, cross calibration of old and new absorptiometers is required. We compared soft tissue estimations from the GE Prodigy (GE Healthcare, Madison, WI) with the more recent iDXA (GE Healthcare) and developed translational equations to enable Prodigy values to be converted to iDXA values. Eighty-three males and females aged 20.1-63.3 yr and with a body mass index range of 17.0-34.4 kg/m2 were recruited for the study. Fifty-nine participants (41 females and 18 males) comprised the cross-calibration group and 24 (14 females and 10 males) comprised the validation group. Total body Prodigy and iDXA scans were performed on each subject within 24 h. Predictive equations for total and regional soft tissue parameters were derived from linear regression of the data. Measures of lean and fat tissues were highly correlated (R2 = 0.95-0.99), but significant differences and variability between machines were identified. Bland-Altman analysis revealed significant biases for most measures, particularly for arm, android, and gynoid fat mass (12.3%-22.7%). The derived translational equations reduced biases and differences for most parameters, although limits of agreement exceeded iDXA least significant change. In conclusion, variability in soft tissue estimates between the Prodigy and iDXA were detected, supporting the need for translational equations in longitudinal monitoring. The derived equations are suitable for group analysis but not individual analysis.


Behavior of susceptible-infected-susceptible epidemics on heterogeneous networks with saturation.
We investigate saturation effects in susceptible-infected-susceptible models of the spread of epidemics in heterogeneous populations. The structure of interactions in the population is represented by networks with connectivity distribution P(k), including scale-free (SF) networks with power law distributions P(k) approximately k(-gamma). Considering cases where the transmission of infection between nodes depends on their connectivity, we introduce a saturation function C(k) which reduces the infection transmission rate lambda across an edge going from a node with high connectivity k. A mean-field approximation with the neglect of degree-degree correlation then leads to a finite threshold lambda(c) >0 for SF networks with 2<gamma</=3. We also find, in this approximation, the fraction of infected individuals among those with degree k for lambda close to lambda(c). We investigate via computer simulation the contact process on a heterogeneous regular lattice and compare the results with those obtained from mean-field theory with and without neglect of degree-degree correlations.


Hyperlactatemia and Cardiac Surgery.
The normal blood lactate level is 0-2 mmol/L, and a value above 3-5 mmol/L is variably used to define hyperlactatemia. In cardiac surgical patients, hyperlactatemia can arise from both hypoxic and non-hypoxic mechanisms. The major non-hypoxic mechanism is likely stress-induced accelerated aerobic metabolism, in which elevated lactate results from a mass effect on the lactate/pyruvate equilibrium. The lactate/pyruvate ratio is normal (<20) in this circumstance. Hyperlactatemia can also result from impaired global or regional oxygen delivery, in which case the lactate/pyruvate ratio is typically elevated (>20). Lactate is a strong anion that is virtually fully dissociated at physiological pH. As such, increased lactate concentration reduces the strong ion difference and exerts an acidifying effect on the blood. Hyperlactatemia in cardiac surgery patients has been categorized as either early or late onset. Early-onset hyperlactatemia is that which develops in the operating room or very early following intensive care unit (ICU) admission. Early-onset hyperlactatemia is strongly associated with adverse outcome and probably arises as a consequence of both hypoxic (e.g., microcirculatory shock) and non-hypoxic (accelerated aerobic metabolism) mechanisms. By contrast, late-onset hyperlactatemia is a benign, self-limiting condition that typically arises within 6-12 hours of ICU admission and spontaneously resolves within 24 hours. Late onset hyperlactatemia occurs in the absence of any evidence of global or regional tissue hypoxia. The mechanism of late onset hyperlactatemia is not understood. Hyperlactatemia is a common accompaniment to treatment with β2-agonists such as epinephrine. Epinephrine-induced hyperlactatemia is thought to be due to accelerated aerobic metabolism and requires no specific intervention. Irrespective of the cause, the presence of hyperlactatemia should trigger a search for remedial causes of impaired tissue oxygenation, bearing in mind that normal-or even supranormal-indices of global oxygen delivery may exist despite regional tissue hypoperfusion.


[Induction of anesthesia using propofol in comparison with etomidate].
Etomidate and propofol were compared for induction of anesthesia in a controlled study, including 24 male patients (ASA groups I and II). Following oral premedication with lormetazepam, the patients received propofol (2.5 mg kg-1; n = 12) or etomidate (0.3 mg kg-1; n = 12) over 60 s. For statistical analysis of the cardiovascular data (blood pressure and heart rate) four blocks were set up: A, baseline value including atropine dosage; B, value after induction of anesthesia; C, value after administration of halothane and vecuronium before intubation; D, value after intubation. The blood pressure fell slightly on administration of propofol while the heart rate remained nearly unchanged. Etomidate was associated with unacceptably high increases in blood pressure and heart rate. Myoclonia occurred in seven patients after etomidate and in two patients after propofol. A smoother mask ventilation was rated as a further advantage of propofol. Because of the unfavorable cardiovascular profile, the occurrence of myoclonia and poor mask ventilation, etomidate proved to be unsuitable for induction of anesthesia unless supplemented by an opioid and/or benzodiazepine. The high incidence of pain upon injection was considered to be a disadvantage of propofol.


[Biological and immunogenic characteristics of Chlamydia trachomatis strain MT-2A (serovar D) and its use for development of experimental inactivated vaccine].
Biological characteristics of C. trachomatis author's strain MT-2A (serovar D) is presented. Stages of development on its basis the experimental formalin-inactivated vaccine against Chlamydia were described. Humoral and cellular immune response to the vaccine administered on 3-dose immunization schedule in conjunction with polyoxidonium as adjuvant was studied. Significant immunological efficacy of the vaccine was shown. T- and B-cell immune responses were characterized. Titer of IgG antibodies against Chlamydia in blood serum after 3rd dose of the vaccine was 10,880+/-1,817.76. Assessment of T-cell response showed that reaction of delayed hypersensitivity with formation of granuloma presented in 60% of animals. Proportion of immunoblasts in reaction of blast-transformation was 29.3+/-2.8%. Perspectives of further studies of the developed corpuscular vaccine against Chlamydia are discussed.


An incidental diagnosis of neurocysticercosis in a dental patient.
Tenia solium, a parasite causes cysticercous cellulose when affecting the central nervous system, the manifestation is called neurocysticercosis. The most common symptom in neurocysticercosis is seizure. Generally, oral diagnosticians come across cases of oral cysticercosis and it is rare to find a case of neurocysticercosis in the dental office, as it goes undetected. Sometimes, when patients experience seizure in the dental office and subsequent evaluation is performed, rarity such as this can be detected. One case of neurocysticercosis in a 27 year old unmarried female patient detected due to its presentation in the dental office is being reported here.


Comparison of the Faran Cylinder Model and the Weak Scattering Model for predicting the frequency dependence of backscatter from human cancellous femur in vitro.
This letter presents the first side-by-side comparison of the Faran Cylinder Model and the Weak Scattering Model for predicting backscatter from human femur. Both models are applied to the same dataset of frequency-dependent backscatter coefficients from 26 human femur cancellous bone samples in vitro. The Faran Cylinder Model predicts a slightly slower rate of increase of backscatter with frequency than the Weak Scattering Model, but both models are in reasonable agreement with the data and with each other, given the uncertainty in the measurements.


NMR provides checklist of generic properties for atomic-scale models of periodic mesoporous silicas.
MCM-41 and SBA-15 silicas were studied by (29)Si solid-state NMR and (15)N NMR in the presence of (15)N-pyridine with the aim to formulate generic structural parameters that may be used as a checklist for atomic-scale structural models of this class of ordered mesoporous materials. High-quality MCM-41 silica constitutes quasi-ideal arrays of uniform-size pores with thin pore walls, while SBA-15 silica has thicker pore walls with framework and surface defects. The numbers of silanol (Q(3)) and silicate (Q(4)) groups were found to be in the ratio of about 1:3 for MCM-41 and about 1:4 for our SBA-15 materials. Combined with the earlier finding that the density of surface silanol groups is about three per nm(2) in MCM-41 (Shenderovich, et al. J. Phys. Chem. B 2003, 107, 11924) this allows us to discriminate between different atomic-scale models of these materials. Neither tridymite nor edingtonite meet both of these requirements. On the basis of the hexagonal pore shape model, the experimental Q(3):Q(4) ratio yields a wall thickness of about 0.95 nm for MCM-41 silica, corresponding to the width of ca. four silica tetrahedra. The arrangement of Q(3) groups at the silica surfaces was analyzed using postsynthesis surface functionalization. It was found that the number of covalent bonds to the surface formed by the functional reagents is affected by the surface morphology. It is concluded that for high-quality MCM-41 silicas the distance between neighboring surface silanol groups is greater than 0.5 nm. As a result, di- and tripodical reagents like (CH(3))(2)Si(OH)(2) and CH(3)Si(OH)(3) can form only one covalent bond to the surface. The residual hydroxyl groups of surface-bonded functional reagents either remain free or interact with other reagent molecules. Accordingly, the number of surface silanol groups at a given MCM-41 or SBA-15 silica may not decrease but increase after treatment with CH(3)Si(OH)(3) reagent. On the other hand, nearly all surface silanol groups could be functionalized when HN(Si(CH(3))(3))(2) was used.


Pulmonary response of severely asthmatic horses after intra-articular administration of methylprednisolone.
Intra-articular (IA) administration of corticosteroids is performed routinely in equine practice. The lung function of severe asthmatic horses has recently been shown to be improved by IA triamcinolone acetonide (TA). We therefore hypothesised that IA methylprednisolone acetate (MPA), another commonly used corticosteroids, would also decrease the airway obstruction in severe asthmatic horses. To compare the effects of intra-articular (IA) and intramuscular (IM) methylprednisolone acetate (MPA) administration on lung function and serum cortisol levels in horses with severe asthma. Randomised and controlled experiments on severe asthmatic research animals. Severe asthmatic horses in exacerbation were administered 200 mg of MPA either intramuscularly (n = 6) or via intra-articular injections in the tarsocrural joints (n = 6; 100 mg/joint). Serum cortisol concentration and pulmonary function was measured for 8 days. A significant decrease in pulmonary resistance in the IA group (P = .003, mean diff 1.14) on day 1 in comparison with baseline was observed. A significant decrease from baseline was also observed on serum cortisol values in the IA group 6 hours after injection (P = .001, mean diff 44.5), and at day 1 (P = .003, mean diff 45.1). Joint health was not evaluated in the current study and the physiological response of the severe asthmatic horses might deviate from that of the milder forms of asthma. MPA IA administration improves the lung function of severe asthmatic horses. However, this effect was mild and of a short duration.


Assembly and Transport of Microscopic Cargos via Reconfigurable Photoactivated Magnetic Microdockers.
The realization of micromotors able to dock and transport microscopic objects in a fluid medium has direct applications toward the delivery of drugs and chemicals in small channels and pores, and the realization of functional wireless microrobots in lab-on-a-chip technology. A simple and general method to tow microscopic particles in water by using remotely controllable light-activated hematite microdockers is demonstrated. These anisotropic ferromagnetic particles can be synthesized in bulk and present the remarkable ability to be activated by light while independently manipulated via external fields. The photoactivation process induces a phoretic flow capable to attract cargos toward the surface of the propellers, while a rotating magnetic field is used to transport the composite particles to any location of the experimental platform. The method allows the assembling of small colloidal clusters of various sizes, composed by a skeleton of mobile magnetic dockers, which cooperatively keep, transport, and release the microscopic cargos. The possibility to easily reconfigure in situ the location of the docker above the cargo is demonstrated, which enables optimize transport and cargo release operations.


Rapid determination of antibiotic resistance in E. coli using dielectrophoresis.
In recent years, infections due to antibiotic-resistant strains of bacteria such as methicillin-resistant Staphylococcus aureus and ciprofloxacin-resistant Escherichia coli are on the rise, and with them the demand for rapid antibiotic testing is also rising. Conventional tests, such as disc diffusion testing, require a primary sample to be tested in the presence of a number of antibiotics to verify which antibiotics suppress growth, which take approximately 24 h to complete and potentially place the patient at severe risk. In this paper we describe the use of dielectrophoresis as a rapid marker of cell death, by detecting changes in the electrophysiology of the cell caused by the administration of an antibiotic. In contrast to other markers, the electrophysiology of the cell changes rapidly during cell death allowing live cells to be distinguished from dead (or dying) cells without the need for culturing. Using polymyxin B as an example antibiotic, our studies indicate that significant changes in cell characteristics can be observed as soon as 1 h passes after isolating a culture from nutrient broth.


Needle localization biopsy of occult lesions of the breast. Experience in 199 cases.
From January 1980 through June 1986, 199 percutaneous needle localizations for clinically occult breast lesions were performed at North Carolina Memorial Hospital. A retrospective analysis of the medical records, mammograms, operative notes, and pathology reports was undertaken to evaluate the success of this procedure. In our series, biopsy was prompted by abnormal calcifications in 27.1% of lesions, occult masses in 37.2%, and by a combination of occult masses and microcalcification in 35.7%. Overall, we had a yield of positive biopsies for cancer of 16.3%, with the yield improving from 12.3% in the earlier years of our study, to 18.7% in the latter years. Of the cancer cases detected, 89.7% were stage I. The localization procedure was successful in 95.9% of the cases. Analysis of our eight failures, along with a review of the literature, shows the major reasons for failure to be incomplete removal of areas with multiple calcifications, dislodgement of the needle, and problems resulting from lack of communication between the radiologist and surgeon. We conclude that the failure rate is low, the yield good, and needle localization a worthwhile procedure for localizing nonpalpable occult lesions.


Treatment Modalities in Calcium Channel Blocker Overdose: A Systematic Review.
Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified approach for treating these patients in the existing literature. This study aimed to assess the effects of different treatment modalities used in calcium channel blocker poisoning, as reported by previous studies. The primary outcomes studied were mortality and hemodynamic parameters after treatment. The secondary outcomes were the length of hospital stay, length of intensive care unit stay, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. A thorough literature search was performed through Ovid, PubMed, Cochrane Library, and Google Scholar from January 2014 to December 31, 2022, to identify all studies analyzing the effects of the treatment of calcium channel blocker poisoning on the desired outcomes. Two reviewers reviewed 607 published articles from January 2014 to December 2022 to identify studies analyzing the effects of the treatment of calcium channel blocker poisoning on desired outcomes. In this review, 18 case reports, one case series, and one cohort study were included. Most patients were treated with an injection of calcium gluconate or calcium chloride. The use of calcium along with dopamine and norepinephrine was found to have lower mortality rates. A few patients were also treated with injection atropine for bradycardia. High-dose insulin therapy was used in 14 patients, of whom two did not survive. In the cohort study, 66 calcium channel blocker toxicity patients were included. These patients were treated with high-dose insulin therapy. A total of 11 patients with calcium channel blocker toxicity succumbed. Although it was found to be associated with improved hemodynamic parameters and lower mortality, side effects such as hypokalemia and hypoglycemia were noted. Intravenous lipid emulsion therapy (administered to eight patients), extracorporeal life support (used in three patients with refractory shock or cardiac arrest), injection glucagon, methylene blue, albumin infusion, and terlipressin were associated with a lower mortality rate as well as improvement in hemodynamic parameters. None of the case reports provided any information on end-organ damage on long-term follow-up.


Text structure and content modulate the recall of patients with dementia of the Alzheimer's type.
Two descriptive and two narrative texts were constructed. The basic forms of each type of text comprised 27 micropropositions, while the detailed forms incorporated an additional 24 micropropositions. Forty DAT patients and 14 control subjects were asked to read and recall the 4 texts and the total number of micropropositions recalled was recorded. Recall performance among DATs was always inferior to that of controls. For both groups, the narrative texts yielded superior recall than the descriptive texts, while the detailed text forms elicited inferior recall than the basic forms. However, the addition of details to the narrative text increased the recall of the basic propositions of DATs, bringing it to similar levels as controls. Results are discussed with reference to the influence of text structure and the situation model on text recall.


Bioavailability of three isoniazid formulations.
The bioavailability of three isoniazid formulations was assessed using a procedure specific for the free drug. Nine human volunteers, all slow acetylators, were each given 4 X 100 mg of isoniazid of three different tablet formulations at weekly intervals; the plasma drug levels were measured at different times during the first 24 hr. No significant differences (p greater than 0.05) were detected among the three products as to relative bioavailability, peak plasma concentrations, Cmax, and the time of Cmax, tmax. Analysis of variance of the pharmacokinetic parameters obtained according to a one-compartment open model did not demonstrate any significant formulation or time effect but revealed a significant intersubject variation in all parameters involved.


Bronchial injury and pneumothorax after reintubation using an airway exchange catheter.
We report a case of pneumothorax caused by a bronchial perforation during a reintubation using an airway exchange catheter (AEC) in a patient with a head and neck cancer. A 53 year old man with oropharynx carcinoma was admitted to ICU for severe pneumonia and severe acute respiratory distress syndrome (ARDS). The patient was recognized as a difficult-to-intubate patient and an endotracheal tube (ETT) was inserted through a bronchoscope. After one week of treatment, it was observed an endotracheal cuff perforation. Exchanging the endotracheal tube was necessary to achieve satisfactory pulmonary ventilation. An AEC Cook 14 was used to perform the reintubation. After reintubation, the patient presented a worsening in oxygen saturation and a chest radiography (CXR) revealed a large pneumothorax. A chest tube was inserted and we observed immediate improvement in oxygen saturation. A repeat CXR confirmed correct positioning of the chest tube and reexpansion of the right lung. A bronchoscopy performed showed a posterior laceration in the right main bronchus. The patient was extubated the following day. After four days, the chest tube was removed. A CXR performed a day after chest tube removal revealed a small right upper pneumothorax, but the patient remained asymptomatic. Airway exchange catheter is a valuable tool to handle with difficult-to-intubate patients. Although the physicians generally focus their attention in avoid barotrauma - caused by oxygen supplement or jet ventilation through AEC - concern for insertion technique can minimize life threatening complications and increase the safety of AEC.


Temporal trends of persistent organic pollutants in dated sediment cores: Chemical fingerprinting of the anthropogenic impacts in the Seine River basin, Paris.
Persistent organic pollutants (POPs) were extensively produced and used throughout the last century. In the early 1980s, a rising concern on the environmental impact of these chemicals has led to the establishment of regulations and changes of use including bans. Long term monitoring of the environmental impacts of these emissions and regulations is a challenge because regular monitoring was not mandatory at the beginning of the first emissions. Moreover, the analytical methods have been strongly improved over the decades. To overcome the lack of monitoring and accurate data, sediment cores are powerful tools to construct contamination records. In this study, a high resolution record was constructed for four POPs families (13 polycyclic aromatic hydrocarbons (PAHs), 15 polychlorinated biphenyls (PCBs), 3 alkylphenols (APs) and 8 polybromodiphenyl ethers (PBDEs)) to establish their historical trends in a long-term urbanized and industrialized environment: the Seine River basin, France. These specific families were selected because they had different sources, uses and histories. The results showed concentrations up to 90 mg/kg for ∑PAHs, 2.3mg/kg for ∑PCB, 1.2mg/kg for ∑APs and 0.06 mg/kg for ∑PBDE. The vertical distribution profiles were different from one family to another and presented a good correlation with uses (e.g. transition from coal to natural gas for PAHs), and regulation implementation (e.g., AP ban after "OSPAR Convention" in 1992). The study of compounds distribution provided original information on sources, e.g. temporal variations in PAH uses. This study demonstrates the usefulness and accuracy of sedimentary archives in floodplain to assess the fate of POPs through time in continental hydrosystems. These first results give a comprehensive overview of the contamination in the Seine River basin downstream of Paris Megacity. They were in good agreement with previous studies dedicated to European areas and highlighted specificities of this basin that were not reported before.


Time, Energy, and Territoriality of the Anna Hummingbird (Calypte anna).
The male Anna Hummingbird accommodates seasonal changes in energy demands by varying its allocation of time and energy among different activities; total energy expenditures change relatively little. Augmented terrritorial defense during the breeding season is made possible by increased feeding efficiency due to the availability at this time of very nectar-rich flowers.


Meta level concept versus classic reflex concept for the control of posture and movement.
Postural reflexes are replaced soon after birth by automatic reactions that allow for volition and cognition. It is still an enigma how this change in postural control is achieved. We suggest that the change involves the formation of a sensory processing level (meta level) that becomes interleaved in between the tight sensor-actuator coupling of the classic reflexes. We assume that the brain applies at this level intersensory interactions to reconstruct the physical stimuli which are causing the physiological stimuli and sensory signals. The thus derived estimates of the physical stimuli are then used as feedback signals in the posture control system. We present this concept on the background of the classic reflex concept and earlier attempts in the literature to overcome it. The earlier attempts were often motivated by the question how the brain prevents voluntary movements from being hampered by reflexive stabilisation of posture (so-called posture-movement problem). We compare our new concept with the classic reflex concept in a theoretical approach, by implementing both concepts into simple postural control models. In simulations of the two models we superimpose external perturbations (the physical stimuli) and a voluntary body lean movement. We show that it is possible to achieve successful stimulus compensation and unperturbed lean movement with both, the model derived from the new concept and the one of the classic reflex concept. With both approaches, the posture-movement problem does not arise. Based on preliminary considerations that include experimental findings from the literature, however, we conclude that the new concept provides more explanatory power than the classic reflex concept.


Mn(OAc)3-mediated phosphonation-lactonization of alkenoic acids: synthesis of phosphono-γ-butyrolactones.
A new, general method for the synthesis of phosphono-γ-butyrolactones has been achieved through Mn(OAc)3-mediated radical oxidative phosphonation and lactonization of alkenoic acids with H-phosphonates and H-phosphine oxide. Mn(OAc)3 can be readily prepared from Mn(OAc)2 in the laboratory. This transformation allows the direct formation of a P-C bond and the construction of a lactone ring in one reaction.


Photoaffinity labeling of Torpedo acetylcholine receptor at multiple sites.
The acetylcholine receptor from Torpedo californica electroplax was labeled with the photoaffinity reagent bis(3-azidopyridinium)decane perchlorate. All four receptor subunits (alpha, beta, gamma, and delta) were specifically labeled. In the presence of cholinergic agonists the gamma-, beta-, and delta-subunit labeling was decreased significantly, whereas labeling of the alpha subunit was minimally affected. Full occupancy of the two high-affinity sites involving the alpha subunits in the vicinity of alpha-Cys-192-Cys-193 by covalent reaction with bromoacetylcholine also caused a large decrease of gamma-subunit labeling by the photoaffinity reagent and lesser but significant decreases in beta- and delta-subunit labeling. No decrease in labeling of the alpha subunit was seen. Labeling of the alpha subunit could, however, be inhibited by high concentrations of the agonist carbamoylcholine. We conclude that the binding sites of high-affinity reside at interfaces of the alpha subunit and other subunits and that the alpha subunit also contributes to formation of a low-affinity site(s) for cholinergic compounds.


Polarization-dependent plasmonic heating in epitaxially grown multilayered metal-organic framework thin films embedded with Ag nanoparticles.
The development of metal-organic framework (MOF) thin films with various functionalities has paved the way for research into a wide variety of applications. MOF-oriented thin films can exhibit anisotropic functionality in the not only out-of-plane but also in-plane directions, making it possible to utilize MOF thin films for more sophisticated applications. However, the functionality of oriented MOF thin films has not been fully exploited, and finding novel anisotropic functionality in oriented MOF thin films should be cultivated. In the present study, we report the first demonstration of polarization-dependent plasmonic heating in a MOF oriented film embedded with Ag nanoparticles (AgNPs), pioneering an anisotropic optical functionality in MOF thin films. Spherical AgNPs exhibit polarization-dependent plasmon-resonance absorption (anisotropic plasmon damping) when incorporated into an anisotropic lattice of MOFs. The anisotropic plasmon resonance results in a polarization-dependent plasmonic heating behavior; the highest elevated temperature was observed in case the polarization of incident light is parallel to the crystallographic axis of the host MOF lattice favorable for the larger plasmon resonance, resulting in polarization-controlled temperature regulation. Such spatially and polarization selective plasmonic heating offered by the use of oriented MOF thin films as a host can pave the way for applications such as efficient reactivation in MOF thin film sensors, partial catalytic reactions in MOF thin film devices, and soft microrobotics in composites with thermo-responsive materials.


Effects of caloric overload before caloric restriction in the murine heart.
The beneficial effects of caloric restriction (CR) against cardiac aging and for prevention of cardiovascular diseases are numerous. However, to our knowledge, there is no scientific evidence about how a high-calorie diet (HCD) background influences the mechanisms underlying CR in whole heart tissue (WHT) in experimental murine models. In the current study, CR-treated mice with different alimentary backgrounds were subjected to transthoracic echocardiographic measurements. WHT was then analyzed to determine cardiac energetics, telomerase activity, the expression of energy-sensing networks, tissue-specific adiponectin, and cardiac precursor/cardiac stem cell markers. Animals with a balanced diet consumption before CR presented marked cardiac remodeling with improved ejection fraction (EF) and fractional shortening (FS), enhanced OXPHOS complex I, III, and IV, and CKMT2 enzymatic activity. Mice fed an HCD before CR presented moderate changes in cardiac geometry with diminished EF and FS values, but improved OXPHOS complex IV and CKMT2 activity. Differences in cardiac remodeling, left ventricular systolic/diastolic performance, and mitochondrial energetics, found in the CR-treated mice with contrasting alimentary backgrounds, were corroborated by inconsistencies in the expression of mitochondrial-biogenesis-related markers and associated regulatory networks. In particular, disruption of eNOS and AMPK -PGC-1α-mTOR-related axes. The impact of a past habit of caloric overload on the effects of CR in the WHT is a scarcely explored subject that requires deeper study in combination with analyses of other tissues and organs at higher levels of organization within the organ system. Such research will eventually lead to the development of preventative and therapeutic strategies to promote health and longevity.


Development and Preclinical Evaluation of Radiolabeled Covalent G12C-Specific Inhibitors for Direct Imaging of the Oncogenic KRAS Mutant.
Although KRAS has been an important target for many cancers, direct inhibition of oncogenic RAS remains challenging. Until recently, covalent KRAS G12C-specific inhibitors have been developed and progressed to the clinics. Nevertheless, not all patients benefit from these covalent inhibitors. At present, identification of candidates for this treatment requires tissue biopsies and gene sequencing, which are invasive, time-consuming, and could be of insufficient quality and limited predictive value owing to tumor heterogeneity. The use of noninvasive molecular imaging techniques such as PET and SPECT for spying KRAS G12C mutation in tumors provide a promising strategy for circumventing these hurdles. In the present study, based on the covalent G12C-specific inhibitor ARS-1620, we sought to develop radiolabeled small molecules for direct imaging of the KRAS mutation status in tumors. [131I]I-ARS-1620 and [18F]F-ARS-1620 were successfully prepared with high radiochemical yield, radiochemical purity, and molar activity. In vitro and in vivo studies have demonstrated the affinity, specificity, and capacity of [131I]I-ARS-1620 for direct imaging of the oncogenic KRAS G12C mutant. This initial attempt allows us to directly screen the KRAS G12C mutant for the first time in vivo.


Pregnancy specific beta 1-glycoprotein and alpha 2-pregnancy associated globulin in tumours of the female genital tract.
Tumour tissues obtained from 35 patients with malignancies of the female genital tract were investigated for production of pregnancy specific beta 1-glycoprotein (PS beta 1G) and alpha 2-pregnancy associated globulin (alpha 2-PAG). PS beta 1G was found in all five trophoblastic tumours studied and in 10 of the 30 nontrophoblastic cancers. alpha 2-PAG was not detected in any of the neoplastic tissues. In 18 of the patients with non-trophoblastic tumours PS beta 1G and alpha 2-PAG serum concentrations were also determined. No correlation between serum and tissue findings were noted. Thus, PS beta 1G does not seem to be a valuable serum indicator for monitoring the extent or variation of tumour mass in nontrophoblastic gynecological malignancies. Likewise, alpha 2-PAG is unlikely to serve as a clinical useful tumour marker in various gynecological cancers.


Idiopathic arterial calcification of infancy: a clinicopathologic study.
The clinical and pathologic features of a group of 62 infants dying of idiopathic calcific arterial disease were reviewed. The disease most commonly occurs in infants less than 6 months of age. Pathologically, it is characterized by calcific deposits along the internal elastic membrane of arteries accompanied by fibrous thickening of the intima which causes luminal narrowing. The arterial lesions are widespread but the resultant luminal narrowing invariably promotes myocardial ischemia, causing the infants' deaths. A definite tendency of the disease to occur in siblings has been noted, but additional patterns of inheritance are not yet apparent. Clinical diagnosis is feasible with radiologic study of arteries of the head, neck, and extremities. There is a similarity of idiopathic calcific arterial disease of infancy to the arterial lesions of metastatic calcification in severe renal disease, calcific arterial lesions noted in conjunction with certain cardiovascular anomalies, and hypervitaminosis D. Certain experimental situations and toxic states can also produce calcific and proliferative vascular lesions.


Intraprocedural left ventricular free wall rupture diagnosed by left ventriculogram in a patient with infero-posterior myocardial infarction and severe aortic stenosis.
Left ventricular wall rupture remains a major lethal complication of acute myocardial infarction and hypertension is a well-known predisposing factor of cardiac rupture after myocardial infarction. An 87-year-old man was admitted to our hospital, diagnosed as acute myocardial infarction (AMI). The echocardiogram showed 0.67-cm(2) aortic valve, consistent with severe aortic stenosis (AS). A coronary angiography showed a chronic occlusion of the proximal left circumflex artery and a 99 % stenosis and thrombus in the mid right coronary artery. During percutaneous angioplasty of the latter, transient hypotension and bradycardia developed at the time of balloon inflation, and low doses of noradrenaline and etilefrine were intravenously administered as needed. The patient suddenly lost consciousness and developed electro-mechanical dissociation. Cardio-pulmonary resuscitation followed by insertion of an intra-aortic balloon pump (IABP) and percutaneous cardiopulmonary support were initiated. The echocardiogram revealed moderate pericardial effusion, though the site of free wall rupture was not distinctly visible. A left ventriculogram clearly showed an infero-posterior apical wall rupture. Surgical treatment was withheld because of the interim development of brain death. In this patient, who presented with severe AS, the administration of catecholamine to stabilize the blood pressure probably increased the intraventricular pressures considerably despite apparently normal measurements of the central aortic pressure. IABP, temporary pacemaker, or both are recommended instead of intravenous catecholamines for patients with AMI complicated with significant AS to stabilize hemodynamic function during angioplasty.


Great doctors and medical worthies.
After Harvey's visits to Scotland with Charles I the formation of a united Caroline University in Aberdeen was thwarted by the Civil War. In Oxford Harvey instituted a group of medical scientists, forerunners of the Royal Society, who almost explained the physiology of respiration. Harvey had several things in common with Dr Samuel Johnson. Johnson's medical knowledge and contacts are emphasised, examples of 17th and 18th century health regimens are given and Johnson's friendship with Scottish medical men and some others connected with the Royal College of Physicians and the Harveian Society of Edingburgh are described.


Effects of Inhaled Salbutamol on Sport-Specific Fitness of Non-Asthmatic Football Players.
In this article, we investigated the effectiveness of inhaled salbutamol withtherapeutic dose on the sport-specific performance of non-asthmatic young football players. In a double-blinded, randomised placebo controlled trial with 2-treatment, 2-period crossover design, twenty participants who were non-asthmatic junior professional football players were randomly allocated to two groups. Fifteen minutes before sport-specific fitness testing, each group randomly received 2 inhalations (200 micrograms) of salbutamol or placebo, respectively. After 1 week wash-out period, each participant has tested again, this time with the alternative inhaler. The primary outcomes were the differences between salbutamol and placebo groups in six tests of 7×30-m repeated sprint, Loughborough soccer dribbling, vertical jump, agility, Loughborough soccer passing, 20-m multistage shuttle run. A total of twenty players did two test batteries completely. There was no significant difference between salbutamol and placebo users in the tests [Treatment effect (CI95%); 7×30 sprint: -2.4 (-7.6-2.9), dribbling: -3.8 (-12.2-4.5), vertical jump: -1.2 (-3.7-1.3), agility: -0.4 (-0.9-0.1), passing: 0.2 (-12-12.4), shuttle run distance: -112 (-503.2-279.2)]. Furthermore, no period or carry-over effects were detected. It seems that single therapeutic dose of inhaled salbutamol (200 micrograms) does not appear to improve football related performance.