Potential treatment with Chinese and Western medicine targeting NSP14 of SARS-CoV-2.
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global health threat. This raises an urgent need for the development of effective drugs against the deadly disease. SARS-CoV-2 non-structural protein 14 (NSP14) carrying RNA cap guanine N7-methyltransferase and 3'-5' exoribonuclease activities could be a potential drug target for intervention. NSP14 of SARS-CoV-2 shares 98.7% of similarity with the one (PDB 5NFY) of acute respiratory syndrome (SARS) by ClustalW. Then, the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14 (PDB 5NFY) as template for virtual screening. Based on the docking score from AutoDock Vina1.1.2, 18 small molecule drugs were selected for further evaluation. Based on the 5 ns MD simulation trajectory, binding free energy (ΔG) was calculated by MM/GBSA method. The calculated binding free energies of Saquinavir, Hypericin, Baicalein and Bromocriptine for the N-terminus of the homology model were -37.2711 ± 3.2160, -30.1746 ± 3.1914, -23.8953 ± 4.4800, and -34.1350 ± 4.3683 kcal/mol, respectively, while the calculated binding free energies were -60.2757 ± 4.7708, -30.9955 ± 2.9975, -46.3099 ± 3.5689, and -59.8104 ± 3.5389 kcal/mol, respectively, when binding to the C-terminus. Thus, the compounds including Saquinavir, Hypericin, Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14, providing a candidate drug against SARS-CoV-2 for further study.


Status of head and neck brachytherapy in Spain in 2022.
Brachytherapy (BT) has been used for many years for disease control in tumours of the head and neck area (H&N). It is currently performed with high dose rate (HDR) or pulsed dose rate (PDR), but its use has been reduced due to the implementation of new non-invasive external beam radiotherapy techniques such as intensity modulation (IMRT) and volumetric modulated arc therapy (VMAT) and the improvement of surgical techniques. The Spanish Brachytherapy Group (GEB) has carried out a survey to find out the number of centres in Spain that continue to use BT in H&N and its indications and expectations for the future. The results were presented at the XX GEB Consensus Meeting held on October 21, 2022, in Valencia (Spain) and it was confirmed that, although there are fewer and fewer centres that use BT in H&N, there are still units with extensive experience in this technique that should be positioned as referral centres. It is necessary to carry out continuous work with other specialities involved, such as H&N surgeons, and other radiation oncologists, to improve the training of residents, both oncologists and medical physicists.


Pro- and antiarrhythmic effects of fast cardiac pacing in a canine model of acquired long QT syndrome.
Increasing the heart rate is one option for suppressing bradycardia-dependent polymorphic ventricular tachycardias (PVTs). The mechanisms underlying preventive pacing in acquired forms of the long QT syndrome (LQTs) are still not fully understood. Using two needle electrodes, local effective refractory periods (ERPs) were determined in the left (LV) and right ventricle (RV) in 20 dogs with acute AV node ablation before continuous pacing, during a 20-min period of continuous fast pacing (Cl 300 ms, fastpac) and during a 35-min recovery period with slow (Cl 500 ms) pacing. This protocol was applied to control dogs (5 dogs) and dogs with pretreatment of the IKs blocking agent chromanol 293b (5 dogs, LQTs1), the IKr-blocking agent dofetilide (5 dogs, LQTs2) or a combination thereof (5 dogs). Fastpac resulted in a significant abbreviation of ERPs in control dogs and dogs receiving dofetilide or chromanol 293b. During recovery, shortening of ERPs persisted in the control group, but diminished in dogs with acquired LQTs. In dogs with LQTs2 fastpac could not suppress inhomogeneity of refractoriness during recovery. With pretreatment of dofetilide and chromanol 293b in combination, MAP duration during fastpac significantly increased (first beat: 256+/-6 ms vs. sixth beat: 278+/-9 ms, p<0.05) and fastpac-induced PVTs were evident. ERP shortening and reduced inhomogeneity of refractoriness might be one antiarrhythmic action of fastpac in dogs with acute AV-block. However, in the acquired LQTs1 and 2 beneficial effects of fastpac diminished and in a combination thereof fastpac-induced PVTs are likely.


Treatment plan comparison between stereotactic body radiation therapy techniques for prostate cancer: non-isocentric CyberKnife versus isocentric RapidArc.
The aim of this study was to evaluate the feasibility and dose distribution of two different stereotactic body radiation therapy (SBRT) techniques, isocentric RapidArc (RA) and non-isocentric CyberKnife (CK), for the treatment of localized prostate cancer. Two groups of patients (Groups 1 and 2 with ten patients per group) treated with CK were re-planned with RA. The patients were grouped according to the rectum constraint used (Group1, maximum dose for rectum; Group 2, dose-volume histogram for rectum). The prescription dose was 37.5 Gy in five fractions. The two SBRT techniques were compared by target coverage, normal tissue sparing, and dose distribution parameters. Monitor units (MUs) and the delivery time were likewise compared to assess delivery efficiency. The RA plans consistently exhibited superior PTV coverage and better rectum sparing at low doses in the both groups. The conformity and heterogeneity indices of the RA plans were better than the CK plans. Additionally, the RA plans resulted in fewer low-dose regions, lower MUs, and faster delivery times than the CK plans. The good dosimetric distribution and shorter delivery time make RA an attractive SBRT technique for the treatment of localized prostate cancer.


Synthesis and characterisation of new silicon-perfluoropropenyl compounds.
Novel, stable silicon-pentafluoropropane compounds have been synthesised from the direct reaction of hydrofluorocarbons Z-CFH[double bond, length as m-dash]CFCF3 (Z-HFC-1225ye) with n BuLi, followed by appropriate silicon-halide. The compounds have been characterized by multinuclear NMR studies (19F, 1H, 29Si and 13C), DFT studies and structural confirmation was obtained by X-ray diffraction. Based on the outcome of treating synthetic silicon-pentafluoropropene compounds with different nucleophilic sources ( n BuLi, t BuLi, MeLi, and PhLi) and computed for this reaction DFT energetics, it is clear that the C-F trans bond is more active than C-F gem (F gem and F trans are labelled with respect to Si). This provides a route for efficient modification of pentafluoropropene group, that can be a crucial step in developing pharmaceuticals that include propenyl or vinyl groups, addressing the demand for medicines based on long carbonic chains.


Algorithm for analysis of OJDIP fluorescence induction curves in terms of photo- and electrochemical events in photosystems of plant cells: derivation and application.
The algorithm for simulation of the OJDIP fluorescence induction curve in chloroplasts under variable conditions is presented. It is derived from analyzes of chlorophyll a fluorescence kinetics upon excitation with single- (STF), twin- (TTF) and repetitive STF excitations, and from the rate equations that describe the sequence of transfer steps associated with the reduction of the primary quinone acceptor Q(A) and the release of photochemical fluorescence quenching of photosystem II (PSII) in multi-turnover excitation (MTF). The fluorescence induction algorithm (FIA) considers a photochemical O-J-D, a photo-electrochemical J-I and an I-P component (phase) which probably is associated with a photo-electric interaction between PSI and PSII. The photochemical phase incorporates the kinetics associated with the double reduction of the acceptor pair [PheQ(A)] in Q(B)-nonreducing reaction centers (RCs) and the associated doubling of the variable fluorescence, in agreement with the three-state trapping model (TSTM) of PSII. Application of and results with the algorithm are illustrated for MTF-induced OJDIP curves, measured in dark-adapted, in STF pre-excited and in DCMU inhibited thylakoids.


Disseminated toxoplasmosis in a heart transplant patient despite co-trimoxazole prophylaxis: A case report.
We report the case of a 61 year-old male who underwent heart transplantation eight months before developing a systemic condition with central nervous system, lung, kidney, colonic, cutaneous, and hematologic involvement, found to be secondary to a systemic toxoplasmosis despite co-trimoxazole prophylaxis in a previous-to-transplant seronegative patient receiving a heart from a seropositive donor. A review of prophylactic options in our environment is discussed.


A new shuttle cosmid vector, pKC505, for streptomycetes: its use in the cloning of three different spiramycin-resistance genes from a Streptomyces ambofaciens library.
A new shuttle cosmid vector, pKC505, was constructed for the cloning of Streptomyces DNA. This vector, which can be conjugally transferred between different streptomycetes, was used to construct a genomic library from a spiramycin-producing S. ambofaciens strain. By transformation of the spiramycin-sensitive S. griseofuscus with the library, three phenotypically different spiramycin-resistance genes were isolated. S. ambofaciens DNA in these clones was colinear with the chromosome, and the cloned DNA was stable in E. coli, S. griseofuscus and S. fradiae. These cosmids could be isolated easily from S. griseofuscus, an improvement over the previous shuttle cosmid vector, pKC462a [Stanzak et al., Bio/Technology 4 (1986) 229-232], which was somewhat difficult to isolate from S. lividans.


The dependency of rheological properties of Plantago lanceolata seed mucilage as a novel source of hydrocolloid on mono- and di-valent salts.
The effects of NaCl and CaCl2 (0-200 mM) on the rheological properties of Plantago lanceolata seed mucilage (PLSM) as a novel potential source of polysaccharide gum were investigated in this study. Furthermore, FTIR analysis was measured to supply more structural information. The FTIR spectra revealed that PLSM with the presence of glycoside bonds and carboxyl and hydroxyl groups behave like a typical polyelectrolyte. It was observed that the gum solutions exhibited viscoelastic properties under the given conditions and the addition of salts had significant affection on the rheological parameters of gum solutions. The weak gel-like behavior (0.1 < tan δ < 1) observed for all solutions at different ion types and ionic strengths. The limiting values of strain mostly increased with enhance cation concentration due to the intermolecular interaction and therefore increase the stiffness of gum solutions in the concentrated domain. The frequency sweep results showed that developing ion concentration had a positive effect on the viscoelasticity of gum solutions which Ca2+ was more effective than Na+. Tanglertpaibul&Rao model showed the highest efficiency to evaluate the intrinsic viscosity of PLSM for all co-solutes. The results of this study could be useful when considering the effects of salts on food systems.


New data on the morphology of Iheringascaris inquies (Linton, 1901) (Nematoda: Anisakidae), a specific parasite of the marine fish Rachycentron canadum (Linnaeus), as revealed by SEM.
Specimens of the type species of the ascaridoid genus Iheringascaris Pereira, 1935, I. inquies (Linton, 1901) (Anisakidae), were collected from the digestive tract and mesentery of its type host Rachycentron canadum (Linnaeus) (Rachycentridae, Perciformes) from off the Atlantic coast of South Carolina, USA, during May of 2011. Scanning electron microscopical examination, used for the first time for specimens originating from the West Atlantic, made it possible to study in detail some taxonomically important morphological features, such as the number and distribution of male caudal papillae, cephalic and cuticular structures, deirids and cloacal (anal) lips. The allocation of other, poorly described, species from different hosts in Indian waters to this genus needs to be confirmed.


The use of metaphyseal sleeves in revision total knee arthroplasty.
Bone loss in revision total knee arthroplasty is common. Various reconstruction options are available. The purpose of our study is to report on one such reconstruction option, titanium metaphyseal sleeves. We describe a series of 45 patients (46 knees) who underwent revision total knee arthroplasty and were treated with a porous metaphyseal sleeve between August 2000 and September 2009 at two centers. Patients were followed for a minimum of four years, and at final follow-up, 40 patients (40 knees) were available for review. Patients were evaluated using The Knee Society's Knee Scoring System at each follow-up. Radiographs (standing anteroposterior, lateral, and sunrise views) were taken at six weeks, three months, and final evaluations. Mean Knee Society Scores increased from 36 (range 10 to 69) pre-operatively to 90 (range 38 to 100) at final follow-up. Mean alignment on final radiographic evaluation was 5° (range 3° to 8° valgus). Mean pre-operative alignment was 6° (range 15° varus to 18° valgus). Mean range of motion was 125° (range 80° to 140°) pre-operatively and 115° (range 95° to 130°) postoperatively. One device failed to achieve ingrowth and was revised at two years. All other knees were radiographically stable and ingrown. Metaphyseal sleeves provide an alternative for bone loss reconstruction in revision total knee arthroplasty. III.


Association of serum uric acid with Pro12Ala polymorphism in PPAR-γ2 among Chinese nonagenarians/centenarians.
In previous studies, Pro12Ala polymorphism in peroxisome proliferator- activated receptors gamma 2 (PPAR-γ2) was shown to be associated with both longevity and metabolic syndrome, which was closely related with hyperuricemia. We examined long-lived subjects (≥90 years), to ascertain whether the polymorphism is associated with the level of serum uric acid (SUA). The present study analysed data from a survey conducted in 2005 on all residents aged 90 years or more in a district with 2,311,709 inhabitants. The sample comprised 669 unrelated Chinese participants (aged 90-108 years, mean: 93.54±3.53 years; 67.2% women). The genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala and 9.0% Pro12Ala, 91.0% Pro12Pro. Between men or women, and between subjects who were or were not 12Ala carriers, neither in SUA levels nor the prevalence of hyperuricemia were significant. Between subjects with and without hyperuricemia, the difference in prevalence of 12Ala carriers was also non-significant. Unadjusted and adjusted multiple logistic regressions showed that the odds ratios (OR) for hyperuricemia were not associated with Pro12Ala polymorphism in PPAR-γ2. In Chinese nonagenarians and centenarians, SUA levels are not associated with polymorphism in PPAR-γ2.


The juvenile gangliosidoses: A timeline of clinical change.
The gangliosidoses are rare inherited diseases that result in pathologic accumulation of gangliosides in the central nervous system and other tissues, leading to severe and progressive neurological impairment and early death in the childhood forms. No treatments are currently approved for the gangliosidoses, and development of treatments is impaired by limited understanding of the natural history of these diseases. The objective of this study is to improve understanding of the juvenile gangliosidoses phenotypes and the late-infantile phenotypic subtype. Through a prospective natural history study of subjects with juvenile GM1- and GM2-gangliosidosis, a timeline of clinical changes was developed for the classic juvenile phenotypes and the late-infantile phenotypes and results of serial neurodevelopmental testing was analyzed. Several candidate 'outcome measures' were identified: changes in ambulation and verbalization skills, the communication domain from neurodevelopmental testing and the caregiver-reported socialization domain. The most common symptoms leading caregivers to seek a genetic diagnosis were changes in ambulation and verbalization.


DFT study of conformational and vibrational characteristics of 2-(2-hydroxyphenyl)benzothiazole molecule.
The conformational and IR and Raman spectral studies of 2-(2-hydroxyphenyl)benzothiazole have been carried out by using the DFT method at the B3LYP/6-311++G(**) level. The detailed vibrational assignments have been done on the basis of calculated potential energy distributions. Comparative studies of molecular geometries, atomic charges and vibrational fundamentals of all the conformers have been made. There are four possible conformers for this molecule. The optimized geometrical parameters obtained by B3LYP/6-311++G(**) method showed good agreement with the experimental X-ray data. The atomic polar tensor (APT) charges, Mulliken atomic charges, natural bond orbital (NBO) analysis and HOMO-LUMO energy gap of HBT and its conformers were also computed.


Technique of lymphatic mapping and sentinel node biopsy for melanoma.
An increasing number of surgeons perform sentinel node biopsy to identify melanoma patients with early lymphatic dissemination who may benefit from regional node dissection or adjuvant therapy. The addition of lymphoscintigraphy and intraoperative gamma-ray detection with a hand-held probe increases the sensitivity of the surgical technique substantially. The value of lymphoscintigraphy is discussed. The operative technique of lymphatic mapping and sentinel node biopsy is described, including the use of a vital dye and a gamma-ray probe. Close to 100% of first-tier lymph nodes can be identified with this combined approach without the unnecessary removal of too many higher-echelon nodes.


Draft genome of six Cuban Anolis lizards and insights into genetic changes during their diversification.
Detecting genomic variants and their accumulation processes during species diversification and adaptive radiation is important for understanding the molecular and genetic basis of evolution. Anolis lizards in the West Indies are good models for studying evolutionary mechanisms because of the repeated evolution of their morphology and the ecology. We performed de novo genome assembly of six Cuban Anolis lizards with different ecomorphs and thermal habitats (Anolis isolepis, Anolis allisoni, Anolis porcatus, Anolis allogus, Anolis homolechis, and Anolis sagrei). We carried out a comparative analysis of these genome assemblies to investigate the genetic changes that occurred during their diversification. We reconstructed novel draft genomes with relatively long scaffolds and high gene completeness, with the scaffold N50 ranging from 5.56 to 39.79 Mb and vertebrate Benchmarking Universal Single-Copy Orthologs completeness ranging from 77.5% to 86.9%. Comparing the repeat element compositions and landscapes revealed differences in the accumulation process between Cuban trunk-crown and trunk-ground species and separate expansions of several families of LINE in each Cuban trunk-ground species. Duplicated gene analysis suggested that the proportional differences in duplicated gene numbers among Cuban Anolis lizards may be associated with differences in their habitat ranges. Additionally, Pairwise Sequentially Markovian Coalescent analysis suggested that the effective population sizes of each species may have been affected by Cuba's geohistory. We provide draft genomes of six Cuban Anolis lizards and detected species and lineage-specific transposon accumulation and gene copy number changes that may be involved in adaptive evolution. The change processes in the past effective population size was also estimated, and the factors involved were inferred. These results provide new insights into the genetic basis of Anolis lizard diversification and are expected to serve as a stepping stone for the further elucidation of their diversification mechanisms.


Gait and electromyographic analysis of patients recovering after limb-saving surgery.
Control of gait after limb-saving surgery.Design. Case series study. At the moment little is known about adaptations in patients' gait after limb-saving surgery. Nineteen patients who underwent limb-saving surgery at least 1 yr earlier and 10 normal subjects were studied during treadmill walking. The main outcome measures were walking speed, step parameters and angular displacement of both legs and EMG of the biceps femoris, rectus femoris and medial gastrocnemius in the affected leg. Preferred walking speed in the patients was lower than in the controls (0.7 versus 1.1 m/s). Furthermore, stance phase of the non-affected leg was lengthened. All patients showed reduced stance phase knee flexion in the affected leg, while during the swing phase no difference was seen. The EMG signals of the rectus femoris and biceps femoris show changes, which are related to the location of surgery. The results showed that the gait pattern of the patients differed compared to normal gait. The reduced stance phase knee flexion in the hip group is based on a high degree of co-contraction between quadriceps and hamstring activity, while in the knee group this is based on the quadriceps avoidance pattern. The finding that there is still side-to-side asymmetry indicates that there is no complete reorganisation following the massive loss of input and output of the leg. It is possible that some reprogramming of the locomotor process occur. Gait and electromyographic analysis are essential for the quantitative assessments of the functional outcome in this type of surgery.


Post-combat syndromes from the Boer war to the Gulf war: a cluster analysis of their nature and attribution.
To discover whether post-combat syndromes have existed after modern wars and what relation they bear to each other. Review of medical and military records of servicemen and cluster analysis of symptoms. Records for 1856 veterans randomly selected from war pension files awarded from 1872 and from the Medical Assessment Programme for Gulf war veterans. Characteristic patterns of symptom clusters and their relation to dependent variables including war, diagnosis, predisposing physical illness, and exposure to combat; and servicemen's changing attributions for post-combat disorders. Three varieties of post-combat disorder were identified-a debility syndrome (associated with the 19th and early 20th centuries), somatic syndrome (related primarily to the first world war), and a neuropsychiatric syndrome (associated with the second world war and the Gulf conflict). The era in which the war occurred was overwhelmingly the best predictor of cluster membership. All modern wars have been associated with a syndrome characterised by unexplained medical symptoms. The form that these assume, the terms used to describe them, and the explanations offered by servicemen and doctors seem to be influenced by advances in medical science, changes in the nature of warfare, and underlying cultural forces.


The (Agri-)Cultural origins of obesity.
Previous research has shown that societies that historically focused on agricultural production demonstrate higher levels of long-term orientation. This suggests that the deep-rooted cultural origins of time preference may have a scarring impact on modern obesity rates through intergenerational transmission. We hypothesize that a historically long-term oriented culture could result in the behavioural choices of better diet and more exercise today, via the reinforced ability of individuals to delay gratification. Using a sample of 132 countries, we employ regression analysis to first estimate the historical determinants of time preference, and then examine the impact of long-term orientation on obesity. Controlling for other factors, we find that, on average, historically long-term oriented countries exhibit significantly lower obesity rates today. Results are robust to different methodological approaches and sensitivity analyses. Policies targeting obesity should consider those deep-rooted behavioural factors that can determine the differential response of individuals to policy instruments.


Effect of an oats-containing gluten-free diet on symptoms and quality of life in coeliac disease. A randomized study.
Evidence suggests the acceptability of oats in a gluten-free diet in coeliac disease. We investigated the impact of an oats-containing diet on quality of life and gastrointestinal symptoms. Thirty-nine coeliac disease patients on a gluten-free diet were randomized to take either 50 g of oats-containing gluten-free products daily or to continue without oats for 1 year. Quality of life was assessed using the Psychological General Well-Being questionnaire and gastrointestinal symptoms using the Gastrointestinal Symptom Rating Scale. Small-bowel mucosal villous architecture, CD3+, alphabeta+, gammadelta+ intraepithelial lymphocytes, serum endomysial and tissue transglutaminase antibodies were investigated. Twenty-three subjects were randomized to the oats-containing diet and 16 to the traditional gluten-free diet. All adhered strictly to their respective diet. Quality of life did not differ between the groups. In general, there were more gastrointestinal symptoms in the oats-consuming group. Patients taking oats suffered significantly more often from diarrhoea, but there was a simultaneous trend towards a more severe average constipation symptom score. The villous structure did not differ between the groups, but the density of intraepithelial lymphocytes was slightly but significantly higher in the oats group. The severity of symptoms was not dependent on the degree of inflammation. Antibody levels did not increase during the study period. The oats-containing gluten-free diet caused more intestinal symptoms than the traditional diet. Mucosal integrity was not disturbed, but more inflammation was evident in the oats group. Oats provide an alternative in the gluten-free diet, but coeliac patients should be aware of the possible increase in intestinal symptoms.


Discrepancy between ACTH and cortisol responses to insulin induced hypoglycaemia.
The purpose of this study was to assess the normal relationship between plasma ACTH and cortisol during insulin induced hypoglycaemia. Twenty-six healthy persons were studied. Peak plasma concentration and the amounts of ACTH and cortisol secreted during hypoglycaemia were compared. There was no significant correlation between the ACTH and cortisol values. The ACTH responses varied significantly more than those of cortisol. This probably signifies an over-capacity of ACTH secretion in comparison to the secretory capacity of the adrenal cortex.


Weight distribution in the sitting position in patients with paralytic scoliosis: pre- and postoperative evaluation.
Patients with paralytic scoliosis spend most of their time in the sitting position. The spinal deformity, pelvic obliquity and uneven weight distribution on the seating surface necessitates frequent seating adaptations in the wheelchair. In this prospective study, 45 wheelchair-bound patients were evaluated preoperatively and 43 postoperatively. The pre- and postoperative evaluation was done by an independent observer. Surgical correction was performed between 1993 and 1996. Assessments included sitting balance on a box; number of seating supports in the wheelchair; weight distribution on the seating surface, measured with a computerized EMED system; Cobb angle; hip dislocation; mediolateral translation of T1 and of the apex vertebra with reference to a perpendicular line drawn upwards from the spinal process of S1; and pelvic obliquity from a line drawn between the most proximal points in the iliac crests. X-rays for the measurement of Cobb angle and pelvic obliquity were performed in sitting position. Reference values for normal weight distribution on the seating surface were obtained for 27 normal subjects and revealed a mean value of 59% of weight supported on one side. A stepwise regression analysis on the preoperative results showed that pelvic obliquity and thoracolumbar/lumbar spinal imbalance explained weight distribution on the seating surface (R(2)=0.45). There were significant improvements in all variables except in sitting balance and imbalance of T1, 1 year postoperatively. When dividing the material into two subgroups, the results showed no significant difference in any of the assessed parameters of the scoliosis, pelvic obliquity, or sitting position between individuals with even (50-59% on one side) and those with uneven (60-100% on one side) weight distribution postoperatively. The results of the assessment showed a significant improvement after surgical correction, but the majority still had pelvic obliquity and uneven weight distribution in a sitting position. The weight distribution on the seating surface preoperatively was explained by thoracolumbar/lumbar spinal imbalance and pelvic obliquity, with R(2)= 0.45. There were no significant differences in any variables in comparisons between individuals with even weight distribution and those with uneven weight distribution. For the group with even weight distribution, however, the mean pelvic obliquity was 6 degrees and in the group with uneven weight distribution the mean pelvic obliquity was 12 degrees. Attention to seating surface and adjustment of seating position is needed for patients with paralytic scoliosis.


Genetic and pathologic findings in a kindred with hereditary sarcoma, breast cancer, brain tumors, leukemia, lung, laryngeal, and adrenal cortical carcinoma.
A familial cancer aggregation comprising sarcomas, brain tumors, leukemias, and carcinomas of breast, larynx, lung, adrenal, cortex, and other sites has been studied from a pathologic--genetic standpoint. Based upon sibships segregating for cancer, the genetic segregation parameter is estimated to be 45.6 +/- 11% which is compatible with that expected for a rare deleterious autosomal gene showing complete dominance. Pathologic review of 16 tumors by bright field microscopy revealed variable occurrences of intranuclear cytoplasmic invaginations, intranucleolar bodies, and acidophilic intracytoplasmic inclusions in eight lesions. Two tumors showed both intranuclear cytoplasmic invaginations and intranucleolar inclusions. Morphological findings coupled with the observed pattern and distribution of cancer in the subject kindred suggest that the cancer-prone genotype interacts with one or more exogenous factors in causing this familial tumor association.


Uterine rupture in a nulliparous woman with septate uterus of the second trimester pregnancy and review in literature.
Uterine rupture (UR) in early pregnancy in nulliparous women is a rare and unpredictable occurrence with high maternal morbidity and fatal fetal outcomes. Intrauterine anomalies could be the primum movens of this dangerous condition and underestimated in the literature. An uncommon case of uterine rupture at the 23rd week of gestation in a nulliparous woman, who became pregnant before the resection of an uterine septum. To provide more insight into the possible risk factors, a literature review was performed. Loss of pregnancy is common, despite prompt uterine repair. In all cases reviewed abdominal pain characterized by indistinct vague symptoms constitutes the initial symptom of this obstetrical life threatening condition. The current case highlights the association of curettage and septate uterus as a risk factor for UR in the second trimester of pregnancy. It's reasonable that obstetricians must take into account that common gastrointestinal tract problems might be an indicator of the initial weakness of uterine wall leading to the rupture, which is unpredictable all of cases reviewed.


Early gastric cancer metastasizing to the rectum, possibly via a hematogenous route: a case report and review of literature.
The most common pattern of recurrence of gastric cancer (GC) is peritoneal dissemination. However, rectal metastasis via hematogenous or lymphatic spread is exceedingly rare. We present a case of a 65-year-old man with an intramucosal GC who developed a rectal recurrence, possibly via a hematogenous route. A 65-year-old man underwent curative endoscopic submucosal dissections for the intramucosal GCs at the anterior wall of the fornix twice. The third GC at the similar location was treated by radical laparoscopic proximal gastrectomy; microscopic examination revealed well-differentiated tubular adenocarcinoma confined to the lamina propria mucosae (T1aN0M0, stage IA). Follow-up colonoscopy revealed a 30-mm submucosal mass in the rectal wall 2 years later, and a metastasis of gastric origin was suspected histopathologically. After a staging laparoscopy confirmed the absence of findings suggestive of serosal involvement or peritoneal dissemination, including negative peritoneal washing cytology, a laparoscopic low anterior resection with lymph node dissection was performed. Microscopically, the tumor was found to mainly be located in the submucosal layer and showed features of moderately differentiated tubular adenocarcinoma. The serosal surface was free of disseminated tumor. Lymph node metastases were identified. Immunohistochemically, there were foci of carcinoma cells that were positive for cytokeratin 20; however, they were negative for cytokeratin 7. Negative staining for caudal-type homeobox 2, a transcription factor indicating goblet cell differentiation, combined with absence of intramucosal carcinoma in the rectal mucosa, suggested a diagnosis of metastatic adenocarcinoma of gastric origin. The absence of evidence of peritoneal dissemination suggested hematogenous or lymphatic spread. Although rectal metastasis from GC, particularly when attributable to hematologic or lymphatic metastasis, is very rare, metastatic gastric adenocarcinoma should be considered as a differential diagnosis for patients who present with a rectal tumor and a past history of GC, even if it is an early GC.


An assessment of the ameliorative role of hesperidin in Drosophila melanogaster model of cadmium chloride-induced toxicity.
Cadmium chloride (CdCl2) is an important heavy metal widely regarded as an environmental contaminant. Hesperidin, a flavanone glycoside found in citrus fruits, has an established properties against free radicals, apoptosis, and inflammation. The present study investigated the protective actions of hesperidin on CdCl2-induced oxidative damage and inflammation in Drosophila melanogaster. For 7 consecutive days via their diet regimen, the flies were exposed to CdCl2 alone (0.05 mM) or in combination with hesperidin (50 and 100 μM). Exposure to CdCl2 significantly (p < 0.05) increased mortality rate of flies, whereas the survived flies demonstrated significant oxidative toxicity from decreased activities of catalase and Glutathione S-transferase (GST) and Total Thiol (T-SH) and Non-Protein Thiols (NPSH) levels as well as accumulation of Nitric Oxide (NO (nitrite/nitrate)), protein carbonyl and Hydrogen Peroxide (H2O2). However, hesperidin-supplemented diet improved Acetylcholinesterase (AChE) activity, mitochondrial metabolic rate (cell viability), locomotor activity, and amelioration of oxidative damage and lipid peroxidation induced by CdCl2. The hesperidin diet supplement boosted the antioxidant milieu and ameliorated the oxidative damage in the treated flies. Overall, the findings revealed that hesperidin improved antioxidative protective capacity in Drosophila melanogaster model of CdCl2-induced toxicity. This suggests hesperidin as a potential therapeutic agent against oxidative stress disorders due to exposure to CdCl2 and or related toxicants.


Demographic and clinical correlates of diabetes-related quality of life among youth with type 1 diabetes.
To evaluate the reliability and cluster structure of the Pediatric Quality of Life Inventory Type 1 Diabetes Module 3.0 (PedsQL-T1DM) and associated subscales and to explore the associations between PedsQL-T1DM total score and demographic and clinical characteristics and clinical indicators among a large racially/ethnically diverse cohort of youth with type 1 diabetes. Principal components analysis was conducted on responses from the PedsQL-T1DM child self-report forms completed by SEARCH for Diabetes in Youth study participants aged ≥ 5 years. Multivariate linear regression models were fit to examine the associations among PedsQL-T1DM total score, demographic and clinical characteristics, and clinical indicators. The sample comprised 2602 youth with a mean age of 13.6 ± 4.1 years and a mean T1DM duration of 62.1 ± 47.0 months. Principal components analysis did not support the 5 existing PedsQL-T1DM subscales. In multivariate analyses, the PedsQL-T1DM total score was negatively and significantly associated with younger age (5-7 years), female sex, receiving insulin by injection (vs pump), having parents without a college degree, Medicaid/Medicare insurance, and having a comorbid medical condition. Youth with poor glycemic control based on their age-specific hemoglobin A1c target values and those with depressive symptoms had significantly lower PedsQL-T1DM scores than their counterparts with good control and no or limited depressive symptoms. This study has identified sociodemographic and clinical characteristics of youth with T1DM more likely to experience poor diabetes-specific quality of life. The association of lower PedsQL-T1DM scores with depressive symptoms and poor glycemic control is especially concerning and may be the focus of future interventions and studies.


[Dental implants and microvascular free fibula flap: 23 patients].
Mandibular reconstruction with a microvascular free fibula flap (MFF) is an elegant solution to restore the anatomic arch, oral functions and facial esthetics. But the thin cutaneous tissue, the thickness of subcutaneous tissues, the absence of a pelvilingual and vestibular groove, and the fragility of soft tissues complicated dental prosthetic retention. Implants may restore prosthetic functionality. There is considerable publication on osteo-integration with a microvascular free fibula flap, but few studies were aimed at the prosthetic aspect, finality of any oral reconstruction. The aim of this retrospective study was to present the results of oral reconstruction with implant supported prostheses after mandibular reconstruction with a microvascular free fibula flap. Twenty-three patients underwent mandibular reconstruction: 17 men and six women with a mean age of 46 years (17-66). Fourteen patients (60.8%) underwent radiotherapy before reconstruction. Mandibular osteoradionecrosis was the indication for reconstruction in seven patients. Each patient was assessed by dentascan. Implants were placed under general anesthesia. Postoperative clinical and radiographic controls were made regularly. Transmucous abutments were placed after six postoperative months and the prosthetic phase was initiated one month later. The criteria for implant and prosthetic success were assessed. Seventy-five implants were placed, on average 3.2 per patient, with an 80% success rate. Three implants (4%) were not used for prosthesis. Ten permanent prostheses and 13 removable prostheses were placed. The mean delay before implant loading was 7.6 months (6-10) and the mean follow-up was 27.5 months (1-71). The occlusion was considered as "satisfactory" for 69.6% of patients. For 57% of patients, the quality of surrounding soft tissues was considered as "satisfactory". For 74% of patients oral reconstruction was "satisfactory". The implant supported prosthesis after MFF mandibular reconstruction, on an irradiated site or not, gives satisfactory results despite the thickness and mobility of soft tissues, and despite scar contracture and the absence of keratinization. Implant placement must be performed after a prosthetic planning. Using radio-surgical guides, despite their cost and difficult adaptation, would certainly bring important improvement to the technique.


Direct force measurement of single DNA-peptide interactions using atomic force microscopy.
The selective interactions between DNA and miniature (39 residues) engineered peptide were directly measured at the single-molecule level by using atomic force microscopy. This peptide (p007) contains an α-helical recognition site similar to leucine zipper GCN4 and specifically recognizes the ATGAC sequence in the DNA with nanomolar affinity. The average rupture force was 42.1 pN, which is similar to the unbinding forces of the digoxigenin-antidigoxigenin complex, one of the strongest interactions in biological systems. The single linear fit of the rupture forces versus the logarithm of pulling rates showed a single energy barrier with a transition state located at 0.74 nm from the bound state. The smaller koff compared with that of other similar systems was presumably due to the increased stability of the helical structure by putative folding residues in p007. This strong sequence-specific DNA-peptide interaction has a potential to be utilized to prepare well-defined mechanically stable DNA-protein hybrid nanostructures.


Evidence for a discontinuous requirement for estrogen in stimulation of deoxyribonucleic acid synthesis in the immature rat uterus.
Estriol is rapidly lost from uterine target cell nuclei. Therefore, it has been used to study the relative time of exposure to estrogen that is necessary to elicit the late growth responses of increased DNA polymerase activity or increased rate of DNA synthesis observed after 17beta-estradiol treatment. Estriol administered during a second critical phase from 9-15 h after the initial injection elicits maximal DNA synthesis. Our results suggest that there is a discontinuous requirement for estrogen in the sequence of events which result in the uterine growth response to estrogenic hormones. If estriol is present during critical phases of this sequence of events, it is equipotent to estradiol in eliciting the full uterotropic response.


Dopamine functionalized tannic-acid-templated mesoporous silica nanoparticles as a new sorbent for the efficient removal of Cu2+ from aqueous solution.
A simple, environmentally friendly and cost-effective nonsurfactant template method was used to synthesize tannic-acid-templated mesoporous silica nanoparticles (TMSNs), and then dopamine functionalized TMSNs (Dop-TMSNs) which was synthesized by a facile and biomimetic coating strategy, was developed as a new sorbent for the removal of Cu2+ from aqueous solution. The Dop-TMSNs were thoroughly characterized by SEM, TEM, BET, FT-IR and TGA, and the effects of contact time, initial pH, K+ and Na+ concentrations, co-existing polyvalent metal ions and adsorption-desorption cycle times on the sorption capacity of Dop-TMSNs were studied. It was demonstrated that the maximum adsorption capacity of Cu2+ by Dop-TMSNs was 58.7 mg/g at pH 5.5, and the sorption reached equilibrium within 180 min. Moreover, the K+ and Na+ concentrations had a very slight influence on the sorption process and the adsorption capacity of the Dop-TMSNs still remained 89.2% after recycling for four times. All the results indicated that the Dop-TMSNs could be utilized as an excellent sorbent for the sequestration of Cu2+.


Climate change and malaria: some recent trends of malaria incidence rates and average annual temperature in selected sub-Saharan African countries from 2000 to 2018.
Malaria is still a disease of massive burden in Africa, also influenced by climate change. The fluctuations and trends of the temperature and precipitation are well-known determinant factors influencing the disease's vectors and incidence rates. This study provides a concise account of malaria trends. It describes the association between average temperature and malaria incidence rates (IR) in nine sub-Saharan African countries: Nigeria, Ethiopia, South Africa, Kenya, Uganda, Ghana, Mozambique, Zambia and Zimbabwe. The incidence of malaria can vary both in areas where the disease is already present, and in regions where it is present in low numbers or absent. The increased vulnerability to the disease under increasing average temperatures and humidity is due to the new optimal level for vector breeding in areas where vector populations and transmission are low, and populations are sensitive due to low acquired immunity. A second source trend analysis was carried out of malaria cases and incidence rates (the number of new malaria cases per 1000 population at risk per year) with data from the World Health Organization (WHO) and average annual mean temperature from 2000 to 2018 from the World Bank's Climate Change Knowledge Portal (CCKP). Additionally, descriptive epidemiological methods were used to describe the development and trends in the selected countries. Furthermore, MS Excel was chosen for data analysis and visualization. Findings obtained from this article align with the recent literature, highlighting a declining trend (20-80%) of malaria IR (incidence rate) from 2000 to 2018. However, malaria IR varies considerably, with high values in Uganda, Mozambique, Nigeria and Zambia, moderate values in Ghana, Zimbabwe, and Kenya, and low values in South Africa and Ethiopia in 2018. Evidence suggests varying IRs after average temperature fluctuations in several countries (e.g., Zimbabwe, Ethiopia). Also, an inverse temperature-IR relationship occurs, the sharp decrease of IR during 2012-2014 and 2000-2003, respectively, occurred with increasing average temperatures in Ghana and Nigeria. The decreasing trends and fluctuations, partly accompanying the temperature, should result from the intervention programmes and rainfall variability. The vulnerability and changing climate could arrest the recent trends of falling IR. Thus, malaria is still a crucial public health issue in sub-Saharan Africa, although a robust decreasing IR occurred in most studied countries.


Retracted: Effects of Individualized Nursing Based on Zero-Defect Theory on Perioperative Patients Undergoing Laparoscopic Cholecystectomy.
[This retracts the article DOI: 10.1155/2022/5086350.].


Orbital rhabdomyosarcoma in a 19-year-old male patient: A case report and literature review.
Rhabdomyosarcoma (RMS) is the most common mesenchymal tumor in children and adolescents, with 10% of cases occurring in the orbits. RMS should be suspected whenever children present with rapidly progressing unilateral exophthalmos. Its symptoms depend on the lesion's origin and location. We report the clinical case of a 19-year-old male patient admitted to the hospital because of blurred vision and bulging eyes that gradually increased over several months. Magnetic resonance imaging showed a mass located mainly in the left orbit, pushing and deforming but not invading the eyeball. The lesion had grown into the left ethmoid sinus wall. The histopathological incisional biopsy results were with alveolar RMS.


Metal organic frameworks as advanced adsorbent materials for separation and analysis of complex samples.
Sample pre-treatment is of great significance for study protein phosphorylation and glycosylation. Due to the low concentration and suppression of matrices, the direct detection of phosphoprotein and glycoprotein by mass spectrometry (MS) are still facing many challenges. The demand of efficient and specific enrichment of phosphoprotein and glycoprotein promotes the sample preparation methods based on metal-organic frameworks (MOFs). In this review, recent advances in MOFs-based samples pre-treatment, including the enrichment of protein, endogenous peptides, glycopeptides, phosphopeptides and glycans are summarized and discussed. In addition, the design and synthesis of different types of MOFs according to different enrichment mechanisms and principles are discussed. Furthermore, the potential problems of sample pre-treatment in proteomics is prospected.


Cost Implications of Insurance Associated Disparities in Post-Acute Traumatic Brain and Spinal Cord Injury Rehabilitation.
Abstract Post-acute care after spinal cord injury (SCI) or traumatic brain injury (TBI) influences neurological function regained. Inpatient rehabilitation facilities (IRFs) have more intensive care and result in lower mortality and better functional outcomes compared with skilled nursing facilities (SNFs). This study sought to quantify inpatient rehabilitation access by insurance and estimate the cost implications. We conducted a retrospective observational cohort study utilizing 2015-2017 California Office of Statewide Health Planning and Development database of injured adults with SCI and/or TBI. The primary predictor was insurance status. The outcome was discharge destination (home, IRFs, SNFs, long-term acute care [LTAC]) modeled using multi-variable multinomial mixed-effects logistic regression controlling for age, diagnosis, Weighted Elixhauser Comorbidity Index, and New Injury Severity Score. Cost of care for discharge to IRFs versus SNFs was estimated by adjusted quantile regression. Cost simulation predicted the adjusted cost difference if all publicly insured participants were discharged to an IRF. We identified 83,230 patients with an injury mechanism and a primary acute care hospitalization diagnosis of TBI (90.9%), SCI (8.3%), or both (0.8%) who were discharged to an IRF, SNF, LTAC, or home. Publicly insured patients were more likely than privately insured patients to go to SNFs versus IRFs (odds ratio [OR]: 2.17, 95% confidence interval [CI 2.01-2.34]). Sub-group analysis of 6416 participants showed an adjusted median total cost difference of $18,461 (95% CI [$5,908-$38,064]) and adjusted cost-per-day of the post-acute encounter of $1,045 (95% CI [$752-$2,399]) higher for discharge to IRFs versus SNFs. Cost simulation demonstrated an additional adjusted cost of $364M annually for universal IRF access for the publicly insured. Publicly insured SCI and TBI Californians are less frequently discharged to IRFs compared with their privately insured counterparts resulting in a lower short-term cost of care. However, the consequences of decreased intensive rehabilitation utilization in terms of functional recovery and long-term cost implications require further investigation.


How can global physical activity surveillance adapt to evolving physical activity guidelines? Needs, challenges and future directions.
Public health guidelines on physical activity (PA) establish national policy agendas and provide the basis for setting goals and targets. Advances in measurement and resulting new scientific findings lead to evolution of PA guidelines. PA surveillance serves to track compliance with national guidelines, usually expressed as the proportion of the population 'meeting' the main quantitative guidelines. The WHO recently completed a process to review and update the global PA guidelines. Changes to the guidelines, such as removal of a 10-min bout criterion, pose challenges for PA surveillance. We review the evolution of PA guidelines and associated surveillance methods and explore implications of the updated guidelines for changes in population surveillance and opportunities for technological approaches to PA to enhance surveillance.


[Focal nodular hyperplasia in a 12-year-old boy: case report and considerations].
Focal nodular hyperplasia (FNH) is a benign hepatic tumor of unknown origin. It is only observed rarely in children (approximately 1-2% of all pediatric liver tumors). A 12-year-old boy who suffered from infectious mononucleosis with liver involvement and hepatomegaly underwent a sonographic scan of the liver at an external hospital 3 months after the infection disappeared which revealed a tumor of the left hepatic lobule. Subsequent further examination (abdominal CT and MRT scans) confirmed the diagnosis of a highly vascularized mass about 10 cm in diameter, suspicious for FNH. Due to the high vascularization no biopsy was performed. A preoperative angiographic coiling and complete surgical resection was carried out because of the size and morphologic uncertainty. The diagnosis of FNH was confirmed by histological examination. The annual sonographic examination at follow-up has been uneventful for a 4-year period. Due to the rarity the diagnosis of FNH in children can be difficult leading to differential diagnostic problems. Due to the risk of bleeding in larger size tumors a biopsy is a point of controversy. Complete resection and histopathological examination of FNHs in childhood is a mandatory therapeutic option, which may be indicated in large tumors or, as in the present case tumors of uncertain biological behaviour.


Impact of comorbidity on survival of Danish prostate cancer patients, 1995-2006: a population-based cohort study.
The existence of comorbid diseases among men with newly diagnosed prostate cancer may affect prostate cancer prognosis. We identified patients (n = 8114) with a first-time discharge diagnosis of prostate cancer from Danish hospitals between 1995 and 2006. We measured comorbidity using the Charlson Comorbidity Index. The number of patients doubled between 1995 and 2006. The proportion of patients with Charlson scores of 0 (no comorbidity) increased from 62% to 63% of total patients diagnosed, whereas the proportion of patients with Charlson scores of 1 to 2 (moderate comorbidity) decreased from 31% to 29%, and the proportion with Charlson scores of 3 or higher (severe comorbidity) increased from 106 to 227 (7% to 8%). Among patients with a Charlson score of 0, the 1-year survival rate improved from 79% to 94%; among patients with Charlson scores of 1 to 2, the 1-year survival rate increased from 68% to 83%; and in patients with a Charlson score of 3 or higher, this rate increased from 61% to 69%. Compared with patients with Charlson scores of 0, patients with scores of 1 to 2 had age-adjusted 1-year mortality rate ratios (MRRs) of 1.60 in 1995 to 1997, increasing to 2.67 in 2004 to 2006. For patients with Charlson scores of 3 or higher, the adjusted MRR increased from 3.11 in 1995 to 1997 to 5.08 in 2004 to 2006. Comorbidity was present in more than one-third of prostate cancer patients and was a negative prognostic factor. Although prostate cancer survival generally has improved in Denmark in recent years, no improvement was found among those with high levels of comorbidity.


Genome-Wide Analysis of Human Long Noncoding RNAs: A Provocative Review.
Do long noncoding RNAs (lncRNAs) contribute little or substantively to human biology? To address how lncRNA loci and their transcripts, structures, interactions, and functions contribute to human traits and disease, we adopt a genome-wide perspective. We intend to provoke alternative interpretation of questionable evidence and thorough inquiry into unsubstantiated claims. We discuss pitfalls of lncRNA experimental and computational methods as well as opposing interpretations of their results. The majority of evidence, we argue, indicates that most lncRNA transcript models reflect transcriptional noise or provide minor regulatory roles, leaving relatively few human lncRNAs that contribute centrally to human development, physiology, or behavior. These important few tend to be spliced and better conserved but lack a simple syntax relating sequence to structure and mechanism, and so resist simple categorization. This genome-wide view should help investigators prioritize individual lncRNAs based on their likely contribution to human biology.


Incidence and prevalence of pediatric onset multiple sclerosis in Kuwait: 1994-2013.
This study aimed to assess the incidence and prevalence of pediatric-onset multiple sclerosis (POMS) along with temporal and gender differentials in these estimates in Kuwait. We identified MS patients with pediatric (age <18 years) onset between 1994 and 2013 from national MS registry. Year and gender-specific incidence rate and prevalence estimates were computed. Multivariable Poisson regression analyses of time-series cross-sectional panel data were conducted to evaluate temporal and gender related variations in yearly POMS incidence rate and prevalence. 122 POMS patients were identified; of which 90 (73.8%) were females. During 2013, POMS incidence rate and prevalence (per 100,000) were 2.1 and 6.0 respectively. Multivariable Poisson regression model revealed statistically significant 5% increase in POMS incidence rate (p=0.002) and 6% increase in prevalence (p<0.001) from 1994 to 2013. Furthermore, during the study period, female children were more likely to have higher POMS incidence rate (relative rate=2.9; p<0.001) and prevalence (prevalence ratio=2.8; p<0.001). The temporal increase and gender disparity in POMS incidence and prevalence corroborate the findings of earlier studies conducted elsewhere. Knowledge of increasing POMS burden may help in optimal planning for better management of patients in the region.


Hyperactivity and depression-like traits in Bax KO mice.
The Bax gene is a member of the Bcl-2 gene family and its pro-apoptotic Bcl-associated X (Bax) protein is believed to be crucial in regulating apoptosis during neuronal development as well as following injury. With the advent of mouse genomics, mice lacking the pro-apoptotic Bax gene (Bax KO) have been extensively used to study how cell death helps to determine synaptic circuitry formation during neurodevelopment and disease. Surprisingly, in spite of its wide use and the association of programmed neuronal death with motor dysfunctions and depression, the effects of Bax deletion on mice spontaneous locomotor activity and depression-like traits are unknown. Here we examine the behavioral characteristics of Bax KO male mice using classical paradigms to evaluate spontaneous locomotor activity and depressive-like responses. In the open field, Bax KO animals exhibited greater locomotor activity than their control littermates. In the forced swimming test, Bax KO mice displayed greater immobility times, a behavior despair state, when compared to controls. Collectively, our findings corroborate the notion that a fine balance between cell survival and death early during development is critical for normal brain function later in life. Furthermore, it points out the importance of considering depressive-like and hyperactivity behavioral phenotypes when conducting neurodevelopmental and other studies using the Bax KO strain.


[FeIII(SR)4]1- complexes can be synthesized by the direct reaction of thiolates with FeCl3.
It is shown that the previously characterized [Fe(III)(SR)(4)](1-) (R=Et, i-Pr, Ph) complexes can be synthesized by the direct reaction of 4equiv. of LiSR with FeCl(3) in DMF solution. [Fe(III)(SR)(4)](1-) complexes are synthetic analogs for the [Fe(III)(S-Cys)(4)] center in rubredoxin proteins.


Ospemifene: first global approval.
Ospemifene (Osphena™) is an oral selective estrogen receptor modulator (SERM), with tissue-specific estrogenic agonist/antagonist effects. QuatRx Pharmaceuticals conducted the global development of the agent before licensing it to Shionogi for regulatory filing and commercialization worldwide. Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy. The drug is approved in the USA, and application for EU regulatory approval is underway. This article summarizes the milestones in the development of ospemifene leading to this first approval for moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy.


Visuo-motor control: when the brain loses track of the eyes.
In single-units studies, neuronal signals are recorded to assess their significance and, hopefully, their role in controlling behavior. A new study of neuronal signals associated with eye position helps to explain not only how the system normally works, but also how it sometimes fails.


Comparative Effectiveness of Adjuvant Chemotherapy in Early-Stage Breast Cancer: A Network Meta-analysis.
There are several regimens recommended by the National Comprehensive Cancer Network (NCCN) for HER2-negative operable breast cancer. To our knowledge, no trials have yet been performed comparing these regimens head to head. We performed a network meta-analysis comparing the efficacy of NCCN-recommended chemotherapy regimens. We searched Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) International Clinical Trials Registry Platform from inception to February 2020. We included randomized clinical trials comparing adjuvant regimens in predominantly node-positive operable breast cancer patients. We compared (1) DDACT, (2) TCx4 cycles, (3) TAC, and (4) ACWKT. Common comparators were (5) AC, (6) ACT, and (7) ACD. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed. The Cochrane risk of bias tool assessed quality of the studies. Odds ratios (ORs) were calculated as measures of treatment effects with AC as reference. We used Bayesian hierarchical random-effects models with noninformative priors for mixed multiple treatment comparisons. Effectiveness was estimated by disease-free and overall survival using ORs. Sensitivity analyses were performed. Safety outcomes included febrile neutropenia. We identified 7 randomized controlled trials with 16,332 patients. TC (odds ratio [95% confidence interval], 0.71 [0.36-1.40]), TAC (0.77 [0.37-1.57]), ACWKT (0.68 [0.34-1.38]), and DDACT (0.72 [0.35-1.42]) were similar for overall survival. TC (0.64 [0.36-1.14]), TAC (0.67 [0.39-1.15]), ACWKT (0.63 [0.37-1.07]), and DDACT (0.59 [0.35-1.01]) had similar disease-free survival benefit. With regard to toxicity, TAC (2.67 [0.30-21.04]) had the highest odds of febrile neutropenia. The current generation of regimens are similar in efficacy. Given the lower toxicity of TCx4 comparatively, it is an acceptable alternative for lower-risk early-stage HER2-negative breast cancers.


Hamartoma of the tuber cinereum in a six-month-old boy, causing isosexual precocious puberty.
A case of hamartoma of the tuber cinereum causing isosexual precocious puberty in a six-month-old boy, in whom the lesion was successfully extirpated, is presented. Our patient was relatively young, since hamartomas causing sexual precocity most often occur between the ages of one and three years. Hamartomas are discussed from the clinical and pathological points of view. The mechanisms of initiating pubertas praecox in cases of cerebral tumours, particularly hamartomas, are reviewed.


Synthesis, characterization and flocculation performance of a novel sodium alginate-based flocculant.
In this study, a natural polymer-based organic flocculant (sodium alginate-methacrylatoethyl trimethyl ammonium chloride, SA-PDMC) was synthesized by graft copolymerization. The optimum preparation procedures were determined by single factor experiments. The flocculation behaviors of SA-PDMC were investigated in humic acid (HA) and kaolin suspension considering the effects of flocculant doses and initial pH. The results indicated that charge neutralization and bridging action played an important role in the removals of HA and kaolin. Also, SA-PDMC performed well in a wide pH range of 5.0-10.0. Besides, SA-PDMC, as polyaluminium (PAC) aid, was investigated in the lake water treatment. The ratio of PAC and SA-PDMC was optimized through response surface methodology based on a central composite design. Results showed that SA-PDMC and PAC have a strong synergy, under optimal conditions SA-PDMC can reduce the dose of PAC by 40 % while ensuring the water quality.


Electrodiagnosis reliability in the diagnosis of infant botulism.
Infant botulism is confirmed by isolation of Clostridium botulinum from stool culture or by toxin assay. Although electrodiagnosis has been described as a diagnostic tool in infant botulism, our 11-year review of toxin-confirmed cases suggests that electrodiagnosis is not a reliable tool. In the case report presented, results of electrodiagnosis were negative but enema effluent contained adequate concentrations of organism and toxin to confirm the diagnosis.


Acute upper airway obstruction following 'staged' bilateral radical neck dissections in previously irradiated patients.
Synchronous bilateral radical neck dissection is generally avoided because of the dramatic oedema that usually ensues. One recommended safer alternative is to perform 'staged' operations. Two case are presented in which acute supraglottic obstruction followed the second neck dissection in patients who had also received radiotherapy to the neck. It is believed that the obstruction was due to swelling following lymphatic destruction secondary to the irradiation, rather than by venous congestion. Some recommendations are made for the management of such cases to avoid this complication.


Characterization of biosurfactant-producing strains of fluorescent pseudomonads in a soilless cultivation system.
The use of biosurfactants is a promising alternative in biological control of zoospore-producing plant pathogens. In the present study, biosurfactant production by the indigenous population of fluorescent pseudomonads in a soilless plant cultivation system was studied during the growing season. A total of 600 strains was screened and of these 18.5% were observed to produce biosurfactants. Production of both antibiotics and biosurfactant was uncommon among the isolated strains. A selective effect of the cultivation system filter was observed on the biosurfactant-producing strains and these strains were only occasionally observed after the filter, despite having a significantly higher motility than the nonbiosurfactant-producing strains. The majority of biosurfactant-producing strains were isolated from the filter skin, which suggests that this is a suitable surface for inoculation with biocontrol strains.


Endoscopic detachable mini-loop ligation for treatment of gastroduodenal angiodysplasia: case study of 11 patients with long-term follow-up.
Detachable mini-loop ligation is useful for endoscopic management of esophageal varices. This study evaluated the treatment of gastroduodenal angiodysplasia by detachable mini-loop ligation. Eleven patients (9 women, 2 men; mean age 61 [18] years) with bleeding gastroduodenal angiodysplasia were treated endoscopically by detachable mini-loop ligation. At endoscopy, two patients had actively bleeding lesions. By using a ligating device, a detachable nylon ring was inserted through the accessory channel of an endoscope and opened at the rim of a transparent ligation chamber attached to the tip of the instrument. The angiodysplasia was aspirated into the chamber, and the mini-loop was closed and detached. Initial ligation therapy was successful in all patients without inducing uncontrollable bleeding. In one patient, two mini-loops were applied to the same angiodysplastic lesion. The only significant complication was severe GI bleeding from a duodenal ulcer that developed at the ligation site in one patient. This was successfully treated by endoscopic placement of hemoclips. Detachable mini-loop ligation is an effective and safe modality for endoscopic treatment of bleeding gastroduodenal angiodysplasia.


G-quadruplex DNA and RNA: Their roles in regulation of DNA replication and other biological functions.
G-quadruplex is one of the best-studied non-B type DNA that is now known to be prevalently present in the genomes of almost all the biological species. Recent studies reveal roles of G-quadruplex (G4) structures in various nucleic acids and chromosome transactions. In this short article, we will first describe recent findings on the roles of G4 in regulation of DNA replication. G4 is involved in regulation of spatio-temporal regulation of DNA replication through interaction with a specific binding protein, Rif1. This regulation is at least partially mediated by generation of specific chromatin architecture through Rif1-G4 interactions. We will also describe recent studies showing the potential roles of G4 in initiation of DNA replication. Next, we will present showcases of highly diversified roles of DNA G4 and RNA G4 in regulation of nucleic acid and chromosome functions. Finally, we will discuss how the formation of cellular G4 could be regulated.


Pulsatile support using a rotary left ventricular assist device with an electrocardiography-synchronized rotational speed control mode for tracking heart rate variability.
We previously developed a novel control system for a continuous-flow left ventricular assist device (LVAD), the EVAHEART, and demonstrated that sufficient pulsatility can be created by increasing its rotational speed in the systolic phase (pulsatile mode) in a normal heart animal model. In the present study, we assessed this system in its reliability and ability to follow heart rate variability. We implanted an EVAHEART via left thoracotomy into five goats for the Study for Fixed Heart Rate with ventricular pacing at 80, 100, 120 and 140 beats/min and six goats for the Study for native heart rhythm. We tested three modes: the circuit clamp, the continuous mode and the pulsatile mode. In the pulsatile mode, rotational speed was increased during the initial 35 % of the RR interval by automatic control based on the electrocardiogram. Pulsatility was evaluated by pulse pressure and dP/dt max of aortic pressure. As a result, comparing the pulsatile mode with the continuous mode, the pulse pressure was 28.5 ± 5.7 vs. 20.3 ± 7.9 mmHg, mean dP/dt max was 775.0 ± 230.5 vs 442.4 ± 184.7 mmHg/s at 80 bpm in the study for fixed heart rate, respectively (P < 0.05). The system successfully determined the heart rate to be 94.6 % in native heart rhythm. Furthermore, pulse pressure was 41.5 ± 7.9 vs. 27.8 ± 5.6 mmHg, mean dP/dt max was 716.2 ± 133.9 vs 405.2 ± 86.0 mmHg/s, respectively (P < 0.01). In conclusion, our newly developed the pulsatile mode for continuous-flow LVADs reliably provided physiological pulsatility with following heart rate variability.


Dickkopf 1 promotes regression of hair follicles.
Recently, we suggested that Dickkopf 1 (DKK-1) is a pathogenic mediator involved in male pattern baldness. As premature catagen onset is a key characteristic of male pattern baldness, in this study, we evaluated whether DKK-1 has a role as a catagen inducer in hair cycling. Herein, we report that recombinant human DKK-1 (rhDKK-1) injection into the hypodermis of mice during anagen caused premature onset of catagen, whereas neutralizing DKK-1 antibody delayed anagen-to-catagen transition in mice. Moreover, treatment with rhDKK-1 led to a decrease in final hair follicle length, whereas DKK-1 antibody led to an increase compared with control animals. In addition, DKK-1 and DKK-1 messenger RNA expression is most upregulated in follicular keratinocytes of late anagen in depilation-induced hair cycle progression. Moreover, we observed that rhDKK-1 blocks canonical Wnt-mediated activation of β-catenin signaling and induces the proapoptotic protein Bax, resulting in apoptosis in outer root sheath keratinocytes. Taken together, our data strongly suggest that DKK-1 is involved in anagen-to-catagen transition in the hair cycle by regulating the activity of follicular keratinocytes.


An analysis of the cosmetic surgery experience acquired through UK plastic surgery training.
Cosmetic surgery is an essential component of Plastic Surgery training. Our study demonstrates the average cosmetic surgery experience of UK Plastic Surgery registrars over their 6-year training scheme. Comparison is made with the operative requirements for the Certificate of Completion of Training (CCT) and the Royal College of Surgeons (RCS) Cosmetic Certification scheme. By using the web-based eLogbook, we analysed all the cosmetic surgery operations recorded by Plastic Surgery registrars during their specialist training. The weighted mean average number of procedures was calculated for different areas of cosmetic surgery practice, according to the level of supervision. The number of RCS cosmetic credits acquired for eight domains of cosmetic surgery was calculated, thus enabling comparison with the operative requirements for certification. eLogbook data were collated for 454 registrars from 2010 to 2016 inclusive. Trainees participated in a mean of 122 cosmetic operations during their training (50% as an assistant), which satisfies the requirement of 100 procedures for CCT. The majority of trainee involvement (66%) was with cosmetic breast and body contouring cases. Comparison with the criteria for cosmetic certification reveals that on average, trainees could certify in cosmetic breast and body contouring surgery but would be unable to accredit in other areas of practice. Current UK training affords sufficient cosmetic surgery exposure for CCT but offers a limited breadth of exposure. Trainees who wish to certify in cosmetic surgery of the head and neck region will likely be required to seek additional experience outside their deanery training programme.


How much of the visual object is used in estimating its position?
Localization accuracy for a wide Gaussian bar (sigma 1 degree) was essentially invariant with sampling density over a wide range. Luminance contrast, on the contrary, had a profound effect on localization accuracy. This difference suggests that the position is estimated from a few (3-4) samples from all those available in the image. A subsequent experiment confirmed that limiting the display to four samples did not impair localization accuracy. Computer simulations show that the result cannot be explained by the peak or centroid rule for position. The results imply that the visual system uses only a few samples to interpolate the luminance profiles, regardless of how many samples are available in the image.


Activity-mode cardiac pacing: clinical considerations.
In the past, pacemaker candidates with "chronotropic incompetence" or chronic atrial arrhythmias have been treated with fixed-rate cardiac pacing. During physical exertion, however, increased cardiac output is often limited by this fixed rate. A physiologic pacemaker that increases the cardiac pacing rate as a response to physical activity is now available. The benefits of this pacemaker are increased heart rate during physical activity and increased exercise tolerance.


Management of Climacturia During Inflatable Penile Prosthesis Surgery.
Radical prostatectomy, the preferred treatment option for organ-confined prostate cancer, is associated with a wide variety of sexual dysfunctions including erectile and orgasmic dysfunctions. Climacturia is a type of orgasmic dysfunction that has been reported to occur in 20-60% of men after radical prostatectomy. Several treatment strategies for climacturia have been evaluated and recommended including behavioral changes, use of special devices, medications, specialized therapies, and surgeries. Inflatable penile prosthesis implantation might be the treatment of choice when conservative management approaches fail to treat erectile dysfunction. In this review article, the different options and approaches for the management of climacturia during inflatable penile prosthesis surgery will be discussed.


Gigantism in unique biogenic magnetite at the Paleocene-Eocene Thermal Maximum.
We report the discovery of exceptionally large biogenic magnetite crystals in clay-rich sediments spanning the Paleocene-Eocene Thermal Maximum (PETM) in a borehole at Ancora, NJ. Aside from previously described abundant bacterial magnetofossils, electron microscopy reveals novel spearhead-like and spindle-like magnetite up to 4 microm long and hexaoctahedral prisms up to 1.4 microm long. Similar to magnetite produced by magnetotactic bacteria, these single-crystal particles exhibit chemical composition, lattice perfection, and oxygen isotopes consistent with an aquatic origin. Electron holography indicates single-domain magnetization despite their large crystal size. We suggest that the development of a thick suboxic zone with high iron bioavailability--a product of dramatic changes in weathering and sedimentation patterns driven by severe global warming--drove diversification of magnetite-forming organisms, likely including eukaryotes.


Outbreak of CTX-M-3-type extended-spectrum beta-lactamase-producing Enterobacter cloacae in a pediatric ward.
A first resistant strain of Enterobacter cloacae was isolated from a blood specimen in a pediatric patient with immature teratoma-developed sepsis after combination chemotherapy. The strain produced extended-spectrum beta-lactamase (ESBL), and the same ESBL-producing strains were detected in urine samples from other patients in the pediatric ward. All strains harbored genes for bla (CTX-M-3) by polymerase chain reaction (PCR) and sequencing analysis. Analysis of pulsed-field gel electrophoresis revealed that all strains were the same clonal type. These results suggest that ESBL-producing strains might be transmitted in the ward via contact among patients or medical staff.


RhopH3, rhoptry gene conserved in the free-living alveolate flagellate Colpodella sp. (Apicomplexa).
In this study, we investigated morphological, immunological and molecular characteristics of Colpodella sp. (American Type Culture Collection 50594) in a diprotist culture containing Bodo caudatus as prey using Plasmodium rhoptry specific antibodies and oligonucleotide primers targeting Plasmodium falciparum rhoptry genes. In culture, Colpodella sp. attached to its prey using the apical end with attachment lasting for approximately 20 min while the cytoplasmic contents of the prey were aspirated into the posterior food vacuole of Colpodella sp. Encystment of Colpodella sp. was observed following feeding. Indirect immunofluorescence assay (IFA) and confocal microscopy using P. falciparum rhoptry specific antibodies showed intense reactivity with cytoplasmic vesicles of Colpodella sp. Bodo caudatus from diprotist and monoprotist (ATCC 30395) cultures showed weak background reactivity. Giemsa staining permitted differentiation of both protists. Genomic DNA isolated from the diprotist culture was used in polymerase chain reaction (PCR) with oligonucleotide primers targeting the P. falciparum rhoptry genes RhopH3, RhopH1/Clag3.2 and RAMA. Primers targeting exon 7 of the P. falciparum RhopH3 gene amplified an approximately 2 kb DNA fragment from the diprotist DNA template. DNA sequence and BLAST search analysis of the amplified product from diprotist DNA identified the RhopH3 gene demonstrating that the RhopH3 gene is conserved in Colpodella sp.


Recovery from Covid-19 smell loss: Two-years of follow up.
To report long-term patterns of recovery and non-recovery in a large nationwide cohort of subjects with COVID-19 associated smell loss. Prospectively, longitudinal questionnaires. Web-based national survey. A longitudinal survey of adults with COVID-19 and/or sudden change in smell or taste since January 1, 2020 was launched April 10, 2020. Participants were queried again in late May 2022 regarding recovery. Data from respondents with >2 years since loss were analyzed and compared to recovery status of those more recently effected. 1103 responded to the survey of whom 946 met inclusion criteria. Among the 267 respondents for whom at least 2 years of follow up was available, 38.2 % reported full recovery, 54.3 % partial, and 7.5 % no recovery. For the entire cohort (all with ≥3 months since smell loss), 38.7 % reported complete recovery, 51.0 % reported partial recovery (ranging from mild complaints to severe phantosmia or dysosmia), and 10.3 % reported no improvement at all. Complete recovery of smell function was significantly higher in those under 40 years old (45.6 % compared to 32.9 % in those over 40). Although the vast majority of subjects who do recover do so within the first 3 months, long-term spontaneous recovery can occur. Rates of recovery do not seem to differ depending on when during the pandemic the loss first occurred.


[Zeolite-containing tripoli powder in experimental hepatology].
Biological activity of zeolite-containing tripoli powder was studied in rats. Biochemical, enzymatic and lipid peroxidation indices were assessed. The results of the study confirm enterosorption and detoxication activity of the powder.


Influence of the pharmacological modification of gastric emptying on lactose digestion and gastrointestinal symptoms.
In lactose maldigesters the ingestion of food which retards gastric emptying improves tolerance to lactose. To study the effects of the pharmacological modification of gastric emptying on the speed of development of lactose-induced symptoms. After an overnight fast, 18 lactose maldigesters were given, in a randomized double-blind study design at 1-week intervals, either propantheline (as bromide 15 mg), metoclopramide (as hydrochloride 10 mg) or placebo, in identical capsules, 60 min before ingesting 50 g lactose coloured with 1 g carmine dye (to measure gastrointestinal transit time). Gastrointestinal symptoms, urinary galactose excretion, and breath hydrogen and blood glucose concentrations were recorded. The propantheline-induced prolongation of gastric emptying improved tolerance to lactose, as measured by reduced area under the gastrointestinal symptom score curve 0-12 h, compared to placebo (by 26%) (P < 0.05) or metoclopramide (by 30%) (P < 0.05). The total hydrogen excretion AUC (180 min follow-up) increased by 15% after metoclopramide as compared with placebo (P = 0.18). Propantheline decreased this variable by 15% from placebo (P = 0.17). No significant differences in blood glucose, urinary galactose or gastrointestinal transit time were found. In an oral lactose tolerance test, delaying gastric emptying with propantheline improved tolerance in lactose maldigesters, as measured by diminished gastrointestinal symptoms and reduced breath hydrogen concentration.


Adolescent non-suicidal self-injury (NSSI) interventions.
Evidence-based treatment of non-suicidal self-injury (NSSI) in adolescents. To review the evidence base supporting current interventions for NSSI. PubMed searches and ancestry analysis. All treatments studied-developmental group therapy, individual cognitive-behavioral therapy, and dialectical behavioral therapy for adolescents-were found to be comparable to the typical treatments offered in the treatment settings where the research was conducted. Additional strategies such as harm reduction have very limited evidence suggesting they may be helpful. A few common interventions including relaxation techniques have extremely limited evidence suggesting they may be perceived as harmful by clients.


Multimodal care for the management of musculoskeletal disorders of the elbow, forearm, wrist and hand: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.
Musculoskeletal disorders of the elbow, forearm, wrist and hand are associated with pain, functional impairment and decreased productivity in the general population. Combining several interventions in a multimodal program of care is reflective of current clinical practice; however there is limited evidence to support its effectiveness. The purpose of our review was to investigate the effectiveness of multimodal care for the management of musculoskeletal disorders of the elbow, forearm, wrist and hand on self-rated recovery, functional recovery, or clinical outcomes in adults or children. We conducted a systematic review of the literature and best evidence synthesis. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials from January 1990 to March 2015. Randomized controlled trials, cohort studies, and case-control studies were eligible. Random pairs of independent reviewers screened studies for relevance and critically appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a low risk of bias were synthesized following best evidence synthesis principles. We screened 5989 articles, and critically appraised eleven articles. Of those, seven had a low risk of bias; one addressed carpal tunnel syndrome and six addressed lateral epicondylitis. Our search did not identify any low risk of bias studies examining the effectiveness of multimodal care for the management of other musculoskeletal disorders of the elbow, forearm, wrist or hand. The evidence suggests that multimodal care for the management of lateral epicondylitis may include education, exercise (strengthening, stretching, occupational exercise), manual therapy (manipulation) and soft tissue therapy (massage). The evidence does not support the use of multimodal care for the management of carpal tunnel syndrome. The current evidence on the effectiveness of multimodal care for musculoskeletal disorders of the elbow, forearm, wrist and hand is limited. The available evidence suggests that there may be a role for multimodal care in the management of patients with persistent lateral epicondylitis. Future research is needed to examine the effectiveness of multimodal care and guide clinical practice. CRD42014009093.


Primary lymphoepithelioma of the esophagus.
A case of primary lymphoepithelioma of the esophagus is presented in an Arabic female patient. This very rare Epstein-Barr virus infection-related malignancy has previously been reported only in patients from Japan. The tumor exhibited classic histologic and immunohistochemical features of lymphoepithelioma, and was successfully treated with neoadjuvant chemotherapy and irradiation followed by surgical resection.


Targeted BCL2 inhibition effectively inhibits neuroblastoma tumour growth.
Genomic aberrations of key regulators of the apoptotic pathway have hardly been identified in neuroblastoma. We detected high BCL2 mRNA and protein levels in the majority of neuroblastoma tumours by Affymetrix expression profiling and Tissue Micro Array analysis. This BCL2 mRNA expression is strongly elevated compared to normal tissues and other malignancies. Most neuroblastoma cell lines lack this high BCL2 expression. Only two neuroblastoma cell lines (KCNR and SJNB12) show BCL2 expression levels representative for neuroblastoma tumours. To validate BCL2 as a therapeutic target in neuroblastoma we employed lentivirally mediated shRNA. Silencing of BCL2 in KCNR and SJNB12 resulted in massive apoptosis, while cell lines with low BCL2 expression were insensitive. Identical results were obtained by treatment of the neuroblastoma cell lines with the small molecule BCL2 inhibitor ABT263, which is currently being clinically evaluated. Combination assays of ABT263 with most classical cytostatics showed strong synergistic responses. Subcutaneous xenografts of a neuroblastoma cell line with high BCL2 expression in NMRI nu/nu mice showed a strong response to ABT263. These findings establish BCL2 as a promising drug target in neuroblastoma and warrant further evaluation of ABT263 and other BCL2 inhibiting drugs.


The Clustering of Lifestyle Behaviours in New Zealand and their Relationship with Optimal Wellbeing.
The purpose of this research was to determine (1) associations between multiple lifestyle behaviours and optimal wellbeing and (2) the extent to which five lifestyle behaviours-sleep, physical activity, sedentary behaviour, sugary drink consumption, and fruit and vegetable intake-cluster in a national sample. A national sample of New Zealand adults participated in a web-based wellbeing survey. Five lifestyle behaviours-sleep, physical activity, sedentary behaviour, sugary drink consumption, and fruit and vegetable intake-were dichotomised into healthy (meets recommendations) and unhealthy (does not meet recommendations) categories. Optimal wellbeing was calculated using a multi-dimensional flourishing scale, and binary logistic regression analysis was used to calculate the relationship between multiple healthy behaviours and optimal wellbeing. Clustering was examined by comparing the observed and expected prevalence rates (O/E) of healthy and unhealthy two-, three-, four-, and five-behaviour combinations. Data from 9425 participants show those engaging in four to five healthy behaviours (23 %) were 4.7 (95 % confidence interval (CI) 3.8-5.7) times more likely to achieve optimal wellbeing compared to those engaging in zero to one healthy behaviour (21 %). Clustering was observed for healthy (5 %, O/E 2.0, 95 % CI 1.8-2.2) and unhealthy (5 %, O/E 2.1, 95 % CI 1.9-2.3) five-behaviour combinations and for four- and three-behaviour combinations. At the two-behaviour level, healthy fruit and vegetable intake clustered with all behaviours, except sleep which did not cluster with any behaviour. Multiple lifestyle behaviours were positively associated with optimal wellbeing. The results show lifestyle behaviours cluster, providing support for multiple behaviour lifestyle-based interventions for optimising wellbeing.


Self-heating of dried wastewater sludge.
We experimentally studied the occurrence of spontaneous self-heating of sludge after drying, to understand its nature, course and remediation. The sludge originates from primary and biological treatment of both municipal and industrial wastewater, the latter largely dominant (approx. 90% total organic carbon, mainly from local tanneries). Dried sludge is collected into big-bags (approx. 1.5m(3)) and landfilled in a dedicated site. After several years of regular operation of the landfill, without any management or environmental issue, indications of local warming emerged, together with smoke and smelling emissions, and local subsidence. During a two year monitoring activity, temperatures locally as high as 80°C have been detected, 6-10 m deep. Experiments were carried out on large quantities of dried sludge (≈ 1t), monitoring the temperature of the samples over long periods of time (months), aiming to reproduce the spontaneous self-heating, under different conditions, to spot enhancing and damping factors. Results demonstrate that air is a key factor to trigger and modulate the self-heating. Water, in addition to air, supports and emphasizes the heating. Unusual drying operation was found to affect dramatically the self-heating activity, up to spontaneous combustion, while ordinary drying conditions yield a sludge with a moderate self-heating inclination. Temperature values as well as heating time scales suggest that the exothermic process nature is mainly chemical and physical, while microbiological activity might be a co-factor.


Idiopathic paresthesia reaction associated with rofecoxib.
To report a case of a paresthesia-type reaction due to the use of rofecoxib in standard doses for the treatment of osteoarthritis. A 55-year-old white woman was receiving rofecoxib for treatment of osteoarthritis. The patient began to have tongue numbness and hand tingling and numbness shortly after starting therapy with rofecoxib. The occurrence and resolution of her symptoms correlated with the start and end of the therapy. An adverse reaction with rofecoxib is a likely explanation for the patient's symptoms. Paresthesias have been reported in 0.1-1.9% of patients who took rofecoxib during premarketing studies, but no causality has been established. One case report of paresthesias occurring in a 59-year-old white man who took one 20-mg dose of piroxicam is available. Information on when the reaction occurred in relation to the dose and resolution of the reaction was not recorded in this study. Our patient's reaction is best classified as idiopathic. We report the first case of a paresthesia-type reaction to rofecoxib in a patient receiving the drug in standard doses for treatment of osteoarthritis. Although the reaction is rare, clinicians should be aware of its potential.


Ultrasonically guided fine needle aspiration biopsy of renal masses.
A consecutive series of 301 ultrasonically guided fine needle aspiration biopsies of renal masses was reviewed. The retrieval rate was 95 per cent and a correct cytological diagnosis was established in 82 per cent of the cases. There were 14 false positive aspirates, for a predictive value of a malignant aspirate of only 93 per cent. All false positive results were misinterpreted as relatively well differentiated adenocarcinoma. We conclude that renal fine needle aspiration biopsy may add information but the risk of a false positive finding must always be considered.


Medical Therapy With Versus Without Revascularization in Stable Patients With Moderate and Severe Ischemia: The Case for Community Equipoise.
All patients with stable ischemic heart disease (SIHD) should be managed with guideline-directed medical therapy (GDMT), which reduces progression of atherosclerosis and prevents coronary thrombosis. Revascularization is also indicated in patients with SIHD and progressive or refractory symptoms, despite medical management. Whether a strategy of routine revascularization (with percutaneous coronary intervention or coronary artery bypass graft surgery as appropriate) plus GDMT reduces rates of death or myocardial infarction, or improves quality of life compared to an initial approach of GDMT alone in patients with substantial ischemia is uncertain. Opinions run strongly on both sides, and evidence may be used to support either approach. Careful review of the data demonstrates the limitations of our current knowledge, resulting in a state of community equipoise. The ongoing ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) is being performed to determine the optimal approach to managing patients with SIHD, moderate-to-severe ischemia, and symptoms that can be controlled medically. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).


Highly sensitive and specific gas chromatographic-tandem mass spectrometric method for the determination of trace amounts of antipyrine metabolites in biological material.
A highly sensitive and specific gas chromatographic-tandem mass spectrometric method was developed for the determination of the antipyrine (INN: phenazone) metabolites, norantipyrine, 4-hydroxyantipyrine and 3-hydroxy-methylantipyrine, in biological material. Deuterated analogues of the metabolites were used as internal standards. The method has a limit of quantitation of 5 ng per sample for the determination of norantipyrine, 4-hydroxy-antipyrine and 3-hyddroxymethylantipyrine with coefficients of variation of 19.4, 14.6 and 20.7%, respectively. Precision and accuracy are good over the whole range measured (5-500 ng/sample) with a coefficient of variation, respectively error of determination < or = 20%. Due to its high sensitivity the method can be used to study the formation of these metabolites in microsomal preparations containing only 100 micrograms of protein.


ACCIDENTAL FINDING OF SYNCHRONOUS BILATERAL DUCTAL CARCINOMA IN SITU IN A YOUNG MAN REFERRED TO MASTECTOMY DUE TO GYNECOMASTIA - AND WHAT IF LIPOSUCTION HAVE BEEN USED? CASE REPORT.
Breast male cancer is a rare condition. We report a case of a synchronous bilateral ductal carcinoma in situ (DCIS) which developed in a 26-year-old man with long-standing gynecomastia. He underwent bilateral subcutaneous mastectomy. Histology revealed bilateral pure DCIS. There was no identifiable causative factor for the development of bilateral DCIS, and there was no family history of the disease. No other treatment was required, and after 18 months there were no signs of local recurrence. This case highlights the importance of staying vigilant regarding the presence of malignancy in normally benign conditions. Liposuction has become a very useful technique for gynecomastia correction, however, there is a risk of dissemination of an unknown malignant tumor. In atypical cases, en bloc surgical excision should be performed.


Predicting tumor response and outcome of second-look surgery with 18F-FDG PET/CT: insights from the GINECO CHIVA phase II trial of neoadjuvant chemotherapy plus nintedanib in stage IIIc-IV FIGO ovarian cancer.
This ancillary study aimed to evaluate 18F-FDG PET parameter changes after one cycle of treatment compared to baseline in patients receiving first-line neoadjuvant anti-angiogenic nintedanib combined to paclitaxel-carboplatin chemotherapy or chemotherapy plus placebo and to evaluate the ability of 18F-FDG PET parameters to predict progression-free survival (PFS), overall survival (OS), and success of second-look surgery. Central review was performed by two readers blinded to the received treatment and to the patients' outcome, in consensus, by computing percentage change in PET metrics within a volume of interest encompassing the entire tumor burden. EORTC and PERCIST criteria were applied to classify patients as responders (partial metabolic response and complete metabolic response) or non-responders (stable metabolic disease and progressive metabolic disease). Also analyzed was the percentage change in metabolic active tumor volume (MATV) and total lesion glycolysis (TLG). Twenty-four patients were included in this ancillary study: 10 received chemotherapy + placebo and 14 chemotherapy + nintedanib. PERCIST and EORTC criteria showed similar discriminative power in predicting PSF and OS. Variation in MATV/TLG did not predict PFS or OS, and no optimal threshold could be found for MATV/TLG for predicting survival. Complete cytoreductive surgery (no residual disease versus residual disease < 0.25 cm/0.25-2.5 cm/> 2.5 cm) was more frequent in responders versus non-responders (P = 0.002 for PERCIST and P = 0.02 for EORTC criteria). No correlation was observed between the variation of PET data and the variation of CA-125 blood level between baseline sample and that performed contemporary to the interim PET, but a statistically significant correlation was observed between ΔSULpeak and ΔCA-125 between baseline sample and that performed after the second cycle. 18F-FDG PET using EORTC or PERCIST criteria appeared to be a useful tool in ovarian cancer trials to analyze early tumor response, and predict second-look surgery outcome and survival. An advantage of PERCIST is the correlation of ΔSULpeak and ΔCA-125, PET response preceding tumor markers response by 1 month. Neither MATV nor TLG was useful in predicting survival. NCT01583322 ARCAGY/ GINECO GROUP GINECO-OV119, 24 April 2012.