Accumulation of radiocarbon in ancient landscapes: A small but significant input of unknown origin.
The persistence of organic carbon (C) in soil is most often considered at timescales ranging from tens to thousands of years, but the study of organic C in paleosols (i.e., ancient, buried soils) suggests that paleosols may have the capacity to preserve organic compounds for tens of millions of years. However, a quantitative assessment of C sources and sinks from these ancient terrestrial landscapes is complicated by additions of geologically modern (~ 10 Ka) C, primarily due to the infiltration of dissolved organic carbon. In this study, we quantified total organic C and radiocarbon activity in samples collected from 28- to 33-million-year-old paleosols that are naturally exposed as unvegetated badlands near eastern Oregon's "Painted Hills". We also used thermal and evolved gas analysis to examine the thermodynamic stability of different pools of C in bulk samples. The study site is part of a ~ 400-m-thick sequence of Eocene-Oligocene (45-28 Ma) paleosols, and thus we expected to find radiocarbon-free samples preserved in deep layers of the lithified, brick-like exposed outcrops. Total organic C, measured in three individual profiles spanning depth transects from the outcrop surface to a 1-m depth, ranged from 0.01 to 0.2 wt% with no clear C-concentration or age-depth profile. Ten radiocarbon dates from the same profiles reveal radiocarbon ages of ~ 11,000-30,000 years BP that unexpectedly indicate additions of potentially modern organic C. A two-endmember mixing model for radiocarbon activity suggests that modern C may compose ~ 0.5-2.4% of the total organic C pool. Thermal and evolved gas analysis showed the presence of two distinct pools of organic C, but there was no direct evidence that C compounds were associated with clay minerals. These results challenge the assumption that ancient badland landscapes are inert and "frozen in time" and instead suggest they readily interact with the modern C cycle.


Chest pain and a left parasternal soft tissue swelling in an immunocompetent refugee with disseminated tuberculosis.
An immunocompetent migrant with chest pain was admitted to an Italian hospital. Computed tomography showed a left pectoral abscess and osteomyelitis of the sternum. The infection had spread into the anterior mediastinum near to the pericardium and the heart, where an atrial mass was confirmed by echocardiography. Disseminated tuberculosis was diagnosed.


Telmisartan attenuates diabetic nephropathy by mitigating oxidative stress and inflammation, and upregulating Nrf2/HO-1 signaling in diabetic rats.
Diabetic nephropathy (DN) is a serious complication of diabetes and can lead to renal failure. Telmisartan (TEL) is an approved angiotensin II type 1 receptor blocker for the treatment of hypertension and possesses nephroprotective efficacy. The study investigated the beneficial effect of TEL on renal oxidative stress, inflammatory response, and apoptosis in type 1 diabetic rats, pointing to the possible role of Nrf2/HO-1 signaling. Diabetes was induced by streptozotocin (STZ), and TEL (5 and 10 mg/kg) was supplement for 8 weeks. TEL ameliorated hyperglycemia, prevented body weight loss and kidney hypertrophy, decreased serum creatinine and urea, and prevented histopathological alterations in diabetic rats. Malondialdehyde (MDA), nitric oxide (NO), NF-κB p65 and TNF-α were increased, whereas GSH, SOD and Bcl-2 were decreased in the kidney of diabetic rats. Treatment with TEL ameliorated oxidative stress, suppressed NF-κB p65 and TNF-α, and boosted cellular antioxidant defenses and Bcl-2. TEL upregulated Nrf2 and HO-1 in the kidney of both normal and diabetic rats. In addition, TEL downregulated VEGF and MMP-9 in the kidney of diabetic rats. In silico molecular docking simulations revealed the potent binding affinity of TEL to NF-κB, MMP-9, Keap1 and HO-1. In conclusion, TEL attenuates DN by ameliorating hyperglycemia, oxidative stress, inflammation, apoptosis and angiogenesis and upregulation of Nrf2/HO-1 signaling.


Percutaneous drainage of abscesses in the postoperative abdomen that is difficult to explore.
We have evaluated our experience with computerized tomography and ultrasonography guided percutaneous drainage of extrahepatic abdominal fluid collections in a group of 22 patients. The most common goal was to avoid or delay surgery on abdomens in which reoperation would be difficult, mainly in high-risk patients. Drainage of pancreatic fluid collections or abscesses was also attempted in a small number of the patients. Percutaneous drainage was curative in 69 percent of those with nonpancreatic abscesses but in only 33 percent of those with abscesses associated with the pancreas. There were no complications attributable to the procedure or to delays in subsequent surgical drainage. Two patients died from problems not directly related to the use of percutaneous drainage. Percutaneous catheter drainage of nonpancreatic abdominal abscesses can play a useful role in patients who are carefully selected because they possess a complex abdominal anatomy distorted by previous surgery and infection or they are at high risk if surgical exploration is carried out.


Reduced economic burden of AIDS-defining illnesses associated with adherence to antiretroviral therapy.
We assessed the economic burden of AIDS-defining illnesses (ADIs), which was further stratified by adherence to antiretroviral therapy (ART). A nationwide longitudinal cohort of 18,234 incident cases with HIV followed for 11years was utilized. Adherence to ART was measured by medication possession ratio (MPR). Generalized estimating equations modeling was used to estimate the cost impact of ADIs. Having opportunistic infections increased the annual cost by 9% (varicella-zoster virus infection) to 98% (cytomegalovirus disease), while the annual costs increased by 26% (Kaposi's sarcoma) to 95% (non-Hodgkin's lymphoma) in the year when AIDS-related cancer occurred. ADIs occurred more frequently in the years with low adherence for ART compared to the high-adherence years (e.g., 0.1≤MPR<0.8 vs. MPR≥0.8, event rate of cytomegalovirus disease 4.03% vs. 0.51%). The annual baseline costs in the years with MPR<0.1, 0.1≤MPR<0.8, and MPR≥0.8 were $250, $4,752, and $8,990 (in 2018 USD), respectively. The economic impact of ADIs in the years with low adherence (MPR<0.1) was larger than that in the high-adherence years (MPR≥0.8) (e.g., MPR<0.1 vs. MPR≥0.8, annual cost increased by 244% vs. 9% when candidiasis occurred). Adherence to ART may increase the baseline medical costs but mitigate the incidence and economic burden of ADIs.


Sequential moderate-dose methotrexate and 5-fluorouracil in advanced gastric adenocarcinoma.
A total of 23 patients with advanced gastric adenocarcinoma were treated with a combination of moderate-dose methotrexate (MDMTX), 250 mg/m2 i.v., with folinic acid rescue and 5-fluorouracil (5-FU) 600 mg/m2 i.v. Therapy was given every 7 days for 4 courses and then at 14-day intervals. All patients were evaluable for response. No complete responses occurred, but five patients (22%) had partial remissions (95% confidence limit, 5%-39%). The median duration of remission was 6 months, with a median survival of 11 months amongst responding patients. In all, six patients (26%) had stable disease for a median period of 5 months. The overall median survival was 6 months. Therapy was generally well tolerated, with principal toxicities consisting of neutropenia, nausea and vomiting, mucositis and diarrhoea. In terms of activity or survival in advanced gastric carcinoma, the combination of moderate-dose MTX and 5-FU does not appear to offer an advantage over single-agent therapy.


[Removal of centrally located subretinal perfluorocarbon liquid].
Subretinal perfluorocarbon liquid (PFCL) droplets are occassionally seen after vitreoretinal surgery for retinal detachment. Usually they are located peripherally without causing complications and therapeutic consequences. In contrast, centrally located PFCL droplets affect final visual outcomes. In animal experiments subretinal PFCL has caused direct toxic effects on photoreceptor cells and retinal pigment epithelium. We report about the rare event of a centrally located subretinal PFCL droplet in 2 patients, their surgical removal and functional outcome. In both patients a PFCL droplet remained subretinally after primary vitrectomy for a rhegmatogenous retinal detachment. In patient 1 the PFCL droplet was located subfoveally for 6 weeks, in patient 2 underneath the papillomacular bundle for 8 weeks causing severe visual loss. In both patients the PFCL was removed transretinally through a 32 gauge cannula. Vision and central scotoma improved in both patients markedly. No complications due to the mini-retinotomy could be observed. Centrally located PFCL droplets are decreasing vision and should be surgically removed. A transretinal removal of subretinal PFCL droplets is possible and the iatrogenic damage seems acceptable.


History of the department of surgery in Cincinnati.
This narrative reviews the foundations and development of surgery in Cincinnati beginning with the surgical pioneers and the founding of the first medical institutions by Dr. Daniel Drake. The amalgamation of multiple medical schools resulted in university affiliation and a "full-time" chairman of surgery. The arrival of Dr. George Heuer and his Johns Hopkins group caused great turmoil but resulted in a strong department of surgery and residency program. Drs. Reid, Carter, and Altemeier succeeded Dr. Heuer and each contributed to the department's growth and success. Dr. Josef E. Fischer became chairman of surgery in 1978 and led the department through difficult times to its greatest expansion and development-bringing to a department with an outstanding history and tradition the reforms and modernizations needed to take it into the 21st century. Dr. Fischer has now returned to Boston and Harvard and was succeeded by Dr. Jeffrey Matthews in 2001. Under his capable leadership the department of surgery at the University of Cincinnati seems assured of a bright future.


Prediagnostic serum 25-hydroxyvitamin D and melanoma risk.
Previous studies of serum 25-hydroxyvitamin D (25(OH)D) in relation to melanoma have shown conflicting results. We conducted a nested case-control study of 708 cases and 708 controls, using prediagnostically collected serum, to study 25(OH)D and melanoma risk in the population-based Janus Serum Bank Cohort. Stratified Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for ultraviolet radiation (UVR) indicators and stratified by ambient UVB of residence and body mass index (BMI). Non-linear associations were studied by restricted cubic splines. Missing data were handled with multiple imputation by chained equations. We found an HR of melanoma risk of 1.01 (95% CI: 0.99, 1.04) and an HRimputed of 1.02 (95% CI: 1.00, 1.04) per 5-nmol/L increase. The spline model showed exposure-risk curves with significantly reduced melanoma risk between 60 and 85 nmol/L 25(OH)D (reference 50 nmol/L). Non-significant J-shaped curves were found in sub-analyses of subjects with high ambient UVB of residence and of subjects with BMI < 25 kg/m2. Our data did not yield persuasive evidence for an association between 25(OH)D and melanoma risk overall. Serum levels within the medium range might be associated with reduced risk, an association possibly mediated by BMI.


Delay in Diagnosis of Duchenne Muscular Dystrophy.
Investigators from Johns Hopkins Hospital, Baltimore, MD, retrospectively reviewed 179 records of patients with Duchenne muscular dystrophy (DMD) evaluated between 1989 and 2012. Diagnosis was confirmed by genetic testing or muscle biopsy, and clinical data were complete in 107 patients.


Influence of postharvest UV-B treatment and fermentation on secondary plant compounds in white cabbage leaves.
The influence of postharvest UV-B on its own and in combination with fermentation (e.g. sauerkraut production) on formation and degradation of bioactive compounds was investigated in white cabbage, processed according to traditional Chinese fermentation methods. The pattern of polyphenols was affected by postharvest UV-B: Newly formed coumaroylglycoside, feruloylglycoside, caffeoylglycoside (up to 1 mg/g dry matter; 4 days) and quercetintriglycoside (0.4-0.5 mg/gdm; 4 days) might be related to postharvest increase in enzyme activity in the biosynthesis. Decreasing contents were observed for the glucosinolates glucobrassicin and 4-methoxyglucobrassicin, but the formation of the degradation products dihydroascorbigen and dihydro-4-methoxyascorbigen, which might be related to cell shrinking as mechanical damage. Fermentation resulted in deglycosidation of hydroxycinnamic acids. Newly generated cinnamic acid from coumaric acid aglycone was detected in fermented plant material combined with UV-B (50 μg/g). Glucosinolates and dihydroascorbigens were completely degraded. This study shows exemplary UV-B as a supplemental step to improve the nutritional quality of processed plants.


Cognitive Dysfunction as a Risk Factor for Psychosis.
The current chapter summarizes recent evidence for cognition as a risk factor for the development of psychosis, including the range of cognitive impairments that exist across the spectrum of psychosis risk symptoms. The chapter examines several possible theories linking cognitive deficits with the development of psychotic symptoms, including evidence that cognitive deficits may be an intermediate risk factor linking genetic and/or neural metrics to psychosis spectrum symptoms. Although there is not strong evidence for unique cognitive markers associated specifically with psychosis compared to other forms of psychopathology, psychotic disorders are generally associated with the greatest severity of cognitive deficits. Cognitive deficits precede the development of psychotic symptoms and may be detectable as early as childhood. Across the psychosis spectrum, both the presence and severity of psychotic symptoms are associated with mild to moderate impairments across cognitive domains, perhaps most consistently for language, cognitive control, and working memory domains. Research generally indicates the size of these cognitive impairments worsens as psychosis symptom severity increases. The chapter points out areas of unclarity and unanswered questions in each of these areas, including regarding the mechanisms contributing to the association between cognition and psychosis, the timing of deficits, and whether any cognitive systems can be identified that function as specific predictors of psychosis risk symptoms.


Melphalan treatment of human peripheral T cells promotes Ig production by B cells in vitro.
Human blood B lymphocytes were cocultured with autologous T lymphocytes which were pretested with melphalan or adriamycin in the presence of pokeweed mitogen (PWM). Melphalan treatment of the cells produced an increased secretion of IgG and IgM, whereas adriamycin did not.


Aortic valve reimplantation in ascending aortic aneurysm: risk factors for early valve failure.
Aortic root reconstruction by reimplantation of the native valve represents a new therapeutic option for ascending aortic aneurysms. Information about long-term follow-up is limited, and possible predictors for failure of reconstruction have not been evaluated so far. After aortic valve reimplantation 101 patients were followed in a prospective observational study. From this cohort the first 75 consecutive patients with a complete 1-year follow-up were chosen for further analysis. Clinical and echocardiographic data were obtained preoperatively, intraoperatively, and early postoperatively, as well as after 1 year of follow-up. No mortality was observed within the first 30 days. There were 52 male patients, mean age was 49.1+/-20.6 years, observation period was 35.6+/-20.6 months, and Marfan's syndrome was present in 22 patients. Although in 67 patients a stable valve function could be demonstrated, 5 patients presented with mild aortic insufficiency or had to be operated on again for secondary valve failure (n = 3). Analyzing possible demographic, disease-related, and procedure-related risk factors in a multivariable approach, only level of coaptation within the graft (as assessed by echocardiography) could be identified as being related to the subsequent development of aortic insufficiency. Coaptation level within the tube graft (type A) resulted in a mean aortic regurgitation grade of 0.3+/-0.5 as compared with a mean grade of 2.5+/-0.6 for a coaptation type C (below the prosthesis; p < 0.001). Aortic valve reimplantation is a promising alternative to alloprosthetic composite replacement. A level of coaptation within the tube graft is essential to achieve valve competence.


Characteristics of Medical Malpractice Claims Involving Temporomandibular Joint Surgery in the United States.
Medical malpractice claims contribute to the practice of defensive medicine which exposes patients to unnecessary tests and limits access to care. The purpose of this study is to characterize medical malpractice claims involving temporomandibular joint (TMJ) operations by oral and maxillofacial surgeons in the United States. Retrospective cross-sectional study of closed medical malpractice claims against oral and maxillofacial surgeons in the Unites States insured by OMS National Insurance Company, RRG (OMSNIC), from January 1, 2016, through December 31, 2020. All claims were obtained from the OMSNIC claims database and classified by procedure type. The primary outcome measure was closed claims involving a TMJ operation. Claims regarding postoperative TMJ complications from non-TMJ operations were excluded. Predictor variables included alleged error and type of TMJ procedure performed. Claim outcome was reported as a secondary outcome measure. Additional outcomes measured included claims involving dentoalveolar or dental implant procedures. Descriptive statistics were performed, and risk ratios were calculated for TMJ claim settlement by alleged error and procedure. Significance was set at P < .05. A total of 1455 closed claims occurred during the study period. There were 14 closed claims involving a TMJ operation (0.96% of all claims). "Improper performance" was the most common alleged error for TMJ claims. Two claims (1 TMJ arthroscopy and 1 TMJ replacement) were settled with payment, and the alleged error for these claims was improper performance. No TMJ claim received a court-adjudicated payout. Dentoalveolar and dental implant-related claims made up 68.73% (n = 1,000) and 15.53% (n = 226) of all OMSNIC claims, respectively. The risk of a settlement was not significantly influenced by alleged error or TMJ procedure performed. Medical malpractice claims against oral and maxillofacial surgeons for TMJ operations are very uncommon. Medical malpractice risk should not factor into a surgeon's decision to exclude TMJ operations from their practice.


Psychiatric resident conceptualizations of mood and affect within the mental status examination.
To explore the ways in which psychiatry residents conceptualize the terms "mood" and "affect," a 14-item questionnaire was sent to residency programs in New York. The questions consisted of possible definitions of mood and affect; all questions required a "true" or "false" response. Residents (N=99) were asked how they viewed mood and affect from a temporal perspective (i.e., sustained versus momentary) and in terms of an objective-subjective (or external-internal) dichotomy. There were inconsistencies in the temporal view of mood (said to be sustained by 60.6% and momentary by 50.5%) and affect ("pervasive" by 26.3% and "momentary" by 66.3%). Residents overwhelmingly defined mood as being subjective and internal and affect as being objective and external. If mood and affect are to be viewed from both perspectives, psychiatrists must infer the enduring internal emotional tone (mood) of a patient over an entire interview.


[Patients on chronic hemodialysis. Hemodynamic study at rest and during exercise before dialysis, in hypertensive and normotensive patients (author's transl)].
In twenty chronic hemodialyzed patients a hemodynamic study was carried out just before dialysis at bed rest and during sitting bicycle exercise. At bed rest, cardiac index (mean +/- standard deviation = 5.2 +/- 1.1/mn/m2) and pulmonary wedge pressure (17.4 +/- 6.8 mmHg) were increased. At the highest level performed (60 ou 90 W) cardiac index increased in all patients and reached on average normal values as compared to normal sedentary subjects, but heart rate less increased than in normal subjects during maximum effort. These data suggest that these patients had no patent heart failure. Pulmonary wedge pressure was more increased in hypertensive patients (20.7 +/- 6.7 mmHg) than in normotensive patients (13.3 +/- 4.4 mmHg). Since cardiac index was similarly increased in both groups of patients the higher values of pulmonary wedge pressure in hypertensive patients could be related to either an increase in total blood volume, or a reduction in left ventricular compliance or an increase in cardiopulmonary blood volume.


Cortical magnetic fields evoked by frequency glides of a continuous tone.
Frequency glides from a continuous tone have been shown to produce activity from the human cortex that can be recorded as time-varying magnetic fields outside the scalp in the same way as simpler auditory stimuli such as clicks and tone bursts. Data analysis has been based on a model assuming an equivalent current dipole localized close to the skull surface. Recorded data have shown good agreement with such a model. Interhemispheric differences have been shown in the location of this dipole, as well as with regard to dipole moment and latencies of responses to contralateral stimulation. The location of the equivalent dipole for frequency glide stimulation is close to that previously reported for tone pulse stimulation. However, the results indicate that differences in location of the order of 10 mm may exist. Comparing previously reported electric responses to frequency glides indicates essentially qualitative agreement although some significant differences have also been found. This is interpreted as evidence that at least the major contributions to the two types of response are produced by the same generator in the temporal lobe of the human cortex.


Influence of sequence and distance between two operators on interaction with the lac repressor.
The influence of additional operator or pseudooperator sequences on the lactose repressor-operator interaction has been investigated. Results of kinetic and equilibrium binding measurements suggest an important in vivo role for the Z-gene pseudooperator in repressor-operator binding; the formation of a ternary, looped complex is indicated by the influence of secondary operator sites on binding parameters. Although the binding affinity of the Z-gene pseudooperator [Oz] is only approximately 1/30 that observed for the primary operator [O], the binding affinity to DNA containing both Oz and O is significantly higher than either sequence alone or the sum of the two. This synergistic effect is enhanced further by replacing the pseudooperator sequence [Oz] with the primary operator sequence and results in an even stronger ternary complex in plasmids with duplicate primary sites. The distance between the center of the two primary operators affects the formation of a ternary complex in the linear DNA molecules. Decreased dissociation rate constants were observed with spacing of operator-like sequences between 300 and 500 base pairs (bp). Minimal influence of the second operator on repressor binding is observed when the operators are separated by approximately 4000 or approximately 100 bp. The significant influence of distance on kinetic and equilibrium parameters was demonstrated by measurements on plasmid pRW1511 [Oi-O-PL-Oz] cleaved with restriction enzymes either in the polylinker region to place Oi-O and Oz on opposite ends of the linear plasmid or outside this region to maintain the sites within 500 bp. These results are consistent with the formation of operator-repressor-pseudooperator ternary complex to generate a looped DNA structure.


The electromotor system of the electric catfish (Malapterurus electricus): a fine-structural analysis.
The electromotor system of the electric catfish (Malapterurus electricus) consists of two large ganglion cells situated in the spinal cord, two single axons containing electric nerves and two large electric organs with several million electroplaque cells. The small, irregularly stacked electroplaque cells possess at their center a crater-like indentation from which a stalk like protrusion arises. Many synaptic contacts derived from a single axon collateral are carried on lobe-like protrusions at the terminal knob of this stalk. The electric nerve consists of a large myelinated axon (diameter: 25 micron) surrounded by many layers of connective tissue cells. The two ganglion cells (200 micron in diameter) are rich in elements of the rough endoplasmic reticulum, Golgi apparatus and lysosomal structures. The cytoplasm of the soma changes its appearance towards the voluminous axon hillock (50 micron in diameter) which these organelles do not enter. The cell soma is perforated in a tunnel-like manner by blood capillaries, axons and processes of glial cells. The cell soma and dendrites are covered with two types of synapse. One type forms mixed chemical and electrical (gap junctions) contacts with intermediate attachment plaques. The other type is only chemical in nature. This system may be useful in the study of an identified vertebrate giant neuron.


Distribution and weathering characteristics of microplastics in paddy soils following long-term mulching: A field study in Southwest China.
Agricultural plastic-film residues have been considered as one of the important sources of microplastics in the agroecosystem. However, limited researches were conducted on the accumulation of microplastics in long-term film-mulched paddy soil. This study aims to investigate the distribution and the weathering characteristics of filmy microplastics in a mulched paddy field (non-mulch, four years of mulched, and ten years of continuous mulched soil were investigated) in Southwest China. More than 50 % of the microplastics in the mulched soil were 1-3 mm, whereas the largest percentage of the microplastics in the non-mulched soil was <1 mm (55.3 %). Microplastic compositions in this field mainly consist of polyester (PES) and polyethylene (PE) (82.1 %). The abundance of microplastics increases with the film mulching time, which were 76.2 ± 18.4, 118.6 ± 44.8, and 159.6 ± 23.5 items kg-1 in soil with non-mulching, four years of mulching, and ten years of continuous mulching, respectively. The filmy microplastics accumulated annually in the plough layer is estimated at 18.1 million items ha-1. Weathering characteristics of filmy microplastics extracted from paddy soil were characterized using FTIR, SEM-EDS, AFM, and contact angle meter. The vinyl, carbonyl, and hydroxyl indices calculated from FTIR results showed that the degradation degree of microplastics incereased as mulching time rose; compared with commercial PE films, the oxygen-containing functional groups of soil-extracted PE films were increased. This study revealed the status of microplastic pollution in paddy soil with long-term mulching. It provided primary data and a scientific basis for further study on environmental behavior and ecological impacts of microplastics in agricultural soils.


Measurement of the intrinsic attenuation of longitudinal waves in anisotropic material from uncorrected raw data.
Among the physical parameters characterising the interaction of the ultrasonic beam with its supporting medium, ultrasonic attenuation is an important input parameter to simulate wave propagation and defect-beam phenomena. The measurement of the intrinsic attenuation in anisotropic material however is a difficult task. The paper presents an approach to determine intrinsic attenuation in anisotropic materials such as austenitic stainless steel welds and cladding. It deals with improvements on the initial device, based on measurements on two samples with different thicknesses (10mm and 20mm). A previous paper presented preliminary results with this new approach for isotropic materials.


[Intra-uterine insemination at either 24 or 48hours after ovulation induction: Pregnancy and birth rates].
Comparing rates of pregnancy and childbirth between IUI at either 24 or 48hours after injection of HCG. This is a single-center retrospective study of couples who underwent intrauterine insemination between January 2013 and December 2014 at Medical-Surgical Obstetrical Centre of Schiltigheim. Stimulation of ovulation was done by FSH or HMG, and ovulation induction by 250μg of recombinant HCG. The insemination was performed after 2 days (group D2) or the day after (group D1). Among the 1092 intrauterine insemination cycles included in our study, 62 were done the day after ovulation induction by HCG (D1), and 1030 the day after (D2). Our study showed no significant difference in the rate of biological pregnancy, defined by a rate of BHCG>15IU/L, between the group D1 (19.35%) and the group D2 (18.12%), P=0.94, and no difference in live birth rate: respectively 14,50% and 11.75%, P=0.18. Our study reported similar rates of pregnancy and childbirth in the group who underwent IUI at D1 and D2 of ovulation induction, suggesting the possibility of IUI on day 1 when the organization of the service needs it, without loss of opportunity for pregnancy.


Serial electrophysiological findings in Guillain-Barré syndrome not fulfilling AIDP or AMAN criteria.
Guillain-Barré syndrome (GBS) is categorized into two major subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). However, a proportion of patients are electrophysiologically unclassified because of electrophysiological findings that do not fulfil AIDP or AMAN criteria, and underlying pathophysiological mechanisms and lesion distributions of unclassified patients are not well defined. The aims of this study are to elucidate disease pathophysiology and lesion distribution in unclassified patients. We retrospectively studied 48 consecutive GBS patients. Patients were classified on the basis of initial electrophysiological findings according to Ho's criteria. Clinical and serial electrophysiological examinations of unclassified patients were conducted. Twelve (25 %) GBS patients were unclassified. All unclassified patients were able to walk independently at 21 days after onset. No unclassified patients, except one patient with diabetes mellitus, had sensory nerve involvement. Eight patients underwent a follow-up study within 15 days of the initial study. Distal motor latencies (DMLs) of the left median motor nerve were found to be significantly and uniformly decreased compared with initial studies (p = 0.008). DMLs (p < 0.0001) and distal compound action potential (CMAP) durations (p = 0.002) of all nerves were significantly decreased, and distal CMAP amplitudes (p = 0.026) significantly increased compared with initial studies. In unclassified GBS patients, DML values during initial electrophysiological studies would be prolonged compared with expected values in the same patient unaffected by GBS and later improve rapidly with increased distal CMAP amplitudes without the development of excessive temporal dispersions. Lesions are also present in distal nerve segments caused by reversible conduction failure.


Bile acids synthesis decreases after laparoscopic sleeve gastrectomy.
Bariatric surgery is the most effective treatment alternative in morbid obesity. The mechanisms contributing to these benefits remain poorly understood. Bile acids (BAs) are mediators of different regulatory functions in glucose and cholesterol homeostasis and energy expenditure. Recent evidence suggests that BAs are critically important for the beneficial effects of sleeve gastrectomy (SG). The aim of this study was to evaluate the effect of SG on BA synthesis. University Hospital. Santiago, Chile. Obese patients were evaluated before and after SG (1, 3, 6, and 12 months). BA synthesis was evaluated through the serum marker, 7 α-hydroxy-4-cholesten-3-one (C4). Primary and secondary BA and C4 were determined by high performance liquid chromatography coupled with tandem mass spectrometry detection (HPLC-MS/MS). From June 2013 to January 2014, 19 patients (age 37.6±7.8 years; BMI 35.8±3.5 kg/m(2); 79% female) were included in this study. Mean weight loss at 1, 3, 6, and 12 months was 11.3, 17.5, 23.6, and 25.4 kg, respectively, equivalent to 11.8, 18.6, 24.8, and 26.9 of total body water percentage (%TBW) (P<.0001), respectively and 43.2, 68.2, 91, and 98.8 of percentage of excess weight loss (%EWL), respectively (P<.001). Serum C4 levels at baseline, 1, 3, 6, and 12 months were 23.4±21.1, 4.9±8.2, 8.7±12.1, 13.8±12.9, and 18.8±16.8 ng/mL (P<.0001), respectively. Fibroblast growth factor 19 (FGF19) levels at baseline, 1, 3, 6, and 12 months were 71±33.3, 130.5±66.2, 117.8±57.2, 134.6±91.7, and 124.3±85.9 pg/mL (P = .019), respectively. Serum levels of C4 decrease after SG, indicating a reduction in the synthesis of BA. FGF19 may play a role in decreasing BA synthesis. Further studies are necessary to characterize the effect of bariatric surgery on BA homeostasis.


Predicting abscesses in adults with community-onset monomicrobial Enterobacteriaceae bacteremia: microorganisms matters.
Enterobacteriaceae is a leading pathogen of community-onset bacteremia. This study aims to establish a predictive scoring algorithm to identify adults with community-onset Enterobacteriaceae bacteremia who are at risk for abscesses. Of the total 1262 adults, 152 (12.0%) with abscess occurrence were noted. The 6 risk factors significantly associated with abscess occurrence-liver cirrhosis, diabetes mellitus, thrombocytopenia and high C-reactive protein (>100 mg/L) at bacteremic onset, delayed defervescence, and bacteremia-causing Klebsiella pneumoniae-were each assigned +1 point to form the scoring algorithm. In contrast, the elderly, fatal comorbidity (McCabe classification), and bacteremia-causing Escherichia coli were each assigned -1 point, owing to their negative associations with abscess occurrence. Using the proposed scoring algorithm, a cut-off value of +1 yielded a high sensitivity (85.5%) and an acceptable specificity (60.4%). Although the proposed predictive model needs further validation, this simple scoring algorithm may be useful for the early identification of abscesses by clinicians.


Cognitive fMRI and soluble telencephalin assessment in patients with localization-related epilepsy.
Objectives - The use of telencephalin as a possible marker for altered cortical function as demonstrated by functional MRI was investigated in a pilot study with 16 patients with localization-related epilepsy and secondarily generalized seizures. Materials and methods - Functional MRI of verbal working memory performance (Sternberg paradigm) and self-regulatory control processes (Stroop paradigm) was used to examine cortical activation in 16 patients with localization-related epilepsy and secondarily generalized seizures. Additionally, blood serum concentrations of soluble telencephalin (marker for neuronal damage) were determined. Results - In three patients (one temporal and two frontal focus), telencephalin was detected. All three patients had lower functional MRI activation in the frontotemporal region (P = 0.04), but not in other regions (P > 0.35) compared with patients without detectable telencephalin. Additionally, an association of levetiracetam and frontotemporal activation was observed. Conclusions - These preliminary data in a heterogeneous group suggest an association between decreased frontotemporal activation on fMRI and both detectable telencephalin serum levels and levetiracetam use. Future longitudinal studies with larger patient groups are required to confirm these observations. It is hypothesized that altered local function of the frontotemporal cortex in localization-related epilepsy might be better predicted by the biochemical marker telencephalin than epilepsy characteristics such as seizure focus.


Studies on contact sensitivity to chromium in the guinea pig. The role of valence in the formation of the antigenic determinant.
Guinea pigs sensitized with either the trivalent chromium chloride or the hexavalent potassium dichromate are capable of reacting in vivo and in vitro to challenges with both chromium salts. This double reactivity is retained also after repeated restimulations with only 1 of these chromium compounds. From the failure to select lymphocytes directed specifically against a chromium determinant of a particular valence it is concluded that by sensitization with chromium salts of different valences a common determinant or closely related determinants are formed. It is suggested that this determinant is formed by chromium in the trivalent form.


Worry and e-cigarette cognition: The moderating role of sex.
As electronic cigarette (e-cigarette) use continues to rise, it is important to identify individual characteristics that may influence e-cigarette use behavior and potential group-level moderators of effects, such as sex. Initial evidence has suggested that worry, defined as excessive, unrealistic thoughts focused on the possibility of future negative events, may contribute to e-cigarette use behavior. Yet, how these established relations differ across groups, such as male and female e-cigarette users, has not been explored. The present study evaluated the effect of worry on perceived barriers for quitting e-cigarettes, perceptions of benefits for e-cigarette use, and perceived negative consequences of e-cigarette use across sex. The sample included 584 current e-cigarette users (52.2% female, Mage = 35.15 years, SD = 10.27). Analyses indicated a significant interaction between sex and worry on each criterion variable (perceived benefits: b = 0.02, SE = 0.01, t = -2.73, p = .01; perceived barriers for quitting e-cigarettes: b = -0.45, SE = 0.08, t = -5.70, p ≤ 0.001; negative consequences to use: b = -0.033, SE = 0.01, t = -4.50, p < .001), such that worry was more strongly related to each outcome among males than females. These findings suggest that sex plays a role in e-cigarette use behaviors and that males may constitute a group that is especially vulnerable to the effects of worry on both positive and negative e-cigarette use perceptions and perceived barriers for quitting e-cigarettes.


Counseling and support services for healthcare workers in German university hospitals during the pandemic-descriptive results of a Germany-wide cross-sectional survey.
Due to the SARS-CoV-2 pandemic, healthcare workers (HCWs) are experiencing tremendous levels of emotional and physical stress. Hospitals are trying to help personnel cope with work-related pressure. The aim of this study was to assess HCWs' awareness and utilization of counseling and support services during the pandemic, HCWs' unmet counseling and support needs, and the type and content of these services. A cross-sectional online survey was conducted from January to June 2021 through the German national research organization Network University Medicine (NUM). All participating hospitals (6 in total) were asked to inform their employees about the study. A total of 1,495 HCWs were included in the analysis. Of these, 42.8% (n = 637) were frontline HCWs (who had contact with COVID-19 patients), 23.1% (n = 344) were second-line HCWs (who only had contact with non-COVID-19 patients) and 34.1% (n = 508) had no contact with any patients. Participating hospitals offer various counseling and support services for their staff. The percentage of respondents who were unaware of available counseling and support services ranged from 5.0 to 42.0%. Depending on the type of counseling and support services, 23.0-53.6% of the respondents indicated that counseling and support services were provided but not used, while 1.7-11.6% indicated that, despite the need for them, such services were not available. HCWs' overall satisfaction with the provided counseling and support services and their unmet support needs differed by patient contact: Frontline HCWs reported more unmet needs for counseling and support than second-line HCWs, while second-line HCWs reported more unmet needs than HCWs without patient contact. The results indicate that hospitals should make more efforts to inform HCWs about available counseling and support services. Hospitals could also create networks where HCWs could share information about the type and content of services and their experiences with various counseling and support services. These steps would enable hospitals to respond more quickly and effectively to the problems facing HCWs during pandemics.


Weak complex formation of adverse drug reaction-associated HLAB57, B58, and B15 molecules.
The combination of certain human leukocyte antigen (HLA) polymorphisms with administration of certain drugs shows a strong correlation with developing drug hypersensitivity. Examples of typical combinations are HLA-B*57:01 with abacavir and HLA-B*15:02 with carbamazepine. However, despite belonging to the same serotype, HLA-B*57:03 and HLA-B*15:01 are not associated with drug hypersensitivity. Recent studies have shown that several HLA polymorphisms are associated with multiple drugs rather than a single drug, all resulting in drug hypersensitivity. In this study, we compared the molecular structures and intracellular localization of HLA-B*57:01, HLA-B*58:01, and HLA-B*15:02, which pose risks for developing drug hypersensitivity, as well as HLA-B*57:03 and HLA-B*15:01 that do not present such risks. We found that HLA molecules posing risks have a low affinity for the subunit β2-microglobulin; notably, the weak hydrogen bond formed via Gln96 of the HLA molecule contributes to this behavior. We also clarified that these HLA molecules are easily accumulated in the endoplasmic reticulum, exhibiting a low expression on the cell surface. Considering that these hypersensitivity risk-associated HLA molecules form complexes with β2-microglobulin and peptides in the endoplasmic reticulum, we assumed that their low complex formation ability in the endoplasmic reticulum facilitates the interaction with multiple drugs.


Destructive effect of DNA topoisomerase II inhibitor vepesid on mouse spermatogenesis.
Inhibition of DNA topoisomerase II with vepesid induced structural and functional reorganization of chromatin in meiotically dividing spermatocytes I, which later led to the block of their differentiation and long-lasting disorders in spermatogenesis. Vepesid induced decondensation of spermatocyte I chromatin, block of desynapsis, and elongation of lateral elements of spermatocyte autosome synaptonemal complexes during late pachytene and diplotene of meiosis. This confirms the involvement of type II DNA topoisomerase in chromatin condensation and homologous chromosome desynapsis at the stage of diplotene and the role of this enzyme in structural organization of the synaptonemal complex. Vepesid induced the formation of dichotomy and breaks of the pericentromer regions of subelements of lateral elements of the autosomal synaptonemal complexes; the number of cells with associations of axial elements of sex chromosomes with autosomal synaptonemal complexes increased, univalents of autosomes and sex chromosomes appeared. Mesna, a modifier of toxic effects of antitumor drugs, had no toxic effect on spermatogenic cells. Mesna reduced the lethal effect of vepesid during combined treatment, but did not ensure long-term protection of spermatogenesis.


A randomized controlled trial with a Canadian electronic pill dispenser used to measure and improve medication adherence in patients with schizophrenia.
Medication adherence is extremely important in preventing relapse and lowering symptoms in schizophrenic patients. However, estimates show that nearly half of these patients have poor adherence. The Brief Adherence Rating Scale (BARS) seems to be the most reliable tool assessing adherence in schizophrenia and shows that the antipsychotic adherence ratio (AAR) is about 49.5% in schizophrenia. The aim of the study was to test if an electronic pill dispenser named DoPill(®) improved AAR of schizophrenic patients. Furthermore, we compared AAR obtained by the DoPill(®) and the BARS, in order to verify whether the DoPill(®) provides reliable assessment of medication adherence. The DoPill(®) is a smart pill dispenser that beeps and flashes at the appropriate time of the day. Each of its 28 compartments is covered by a plastic lamina that, when taken off, sends a signal to the pharmacist. Patients were randomized to the DoPill(®) or treatment as usual groups for 6 weeks. The BARS was used as a reference measure. Forty-six percent of patients were deemed to be non-adherent with antipsychotic medication. The mean AAR was 67% after 6 weeks. DoPill(®) recorded better AAR than some of those found in the literature and were lower than the BARS estimate we found. These results suggest that DoPill(®) is a valid tool that provides more reliable and objective data for the clinician about their patient's adherence, than existing assessment tools like the BARS. Furthermore, the device may help patients successfully manage their medication regimen.


Breastfeeding patterns and risk of childhood acute lymphoblastic leukaemia.
The risk of childhood acute lymphoblastic leukaemia (ALL) was investigated in relation to breastfeeding patterns in the Northern California Childhood Leukaemia Study. Data collected by self-administered and in-person questionnaires from biological mothers of leukaemia cases (age 0-14 years) in the period 1995-2002 were matched to birth certificate controls on date of birth, sex, Hispanic ethnic status, and maternal race. Ever compared to never breastfeeding was not associated with risk of ALL at ages 1-14 years (odds ratio=0.99; 95% CI=0.64-1.55) and ages 2-5 years (OR=1.49; 95% CI=0.83-2.65). Various measures of breastfeeding duration compared to absence of breastfeeding also had no significant effect on risk. Complimentary feeding characteristics such as type of milk/formula used and age started eating solid foods among breastfed children were not associated with ALL risk. This study provides no evidence that breastfeeding affects the occurrence of childhood ALL.


Developmental kinetics of in vitro-produced bovine embryos: An aid for making decisions.
Embryo developmental kinetics and embryo survival after cryopreservation have been correlated with embryo quality and viability. The main objectives of this work were to analyze developmental ability and quality of in vitro-produced bovine embryos in relation to their kinetics and to establish a criterion of quality to predict further viability. Embryos were classified and grouped by their specific stage of development (2, 3-4, or ≥ 5 cells) at 44 hours post insemination (hpi) and cultured separately up to Day 8. On Days 7 and 8, good quality expanded blastocysts were vitrified or frozen. Cryopreserved surviving hatched embryos were stained for cell counts. Embryos at a more advanced stage (3-4 cells, and ≥5 cells) developed to morulae (P < 0.001) and blastocysts (P < 0.01) at higher rates than those embryos that had cleaved once by 44 hpi. Vitrification improved the hatching rates of blastocysts at 48 hours (P < 0.001) when compared with slow-rate freezing within each group of embryos (3-4 cells and ≥5 cells). After vitrification/warming, blastocysts coming from 3- to 4-cell embryos had higher hatching rates at 48 hours than those that came from ≥5-cell embryos. With regard to differential cell counts, no effect of the initial developmental stage was observed after warming/thawing. However, trophectoderm and total cells were higher in vitrified/warmed than in the frozen/thawed embryos (P < 0.001). These data show that selecting IVF embryos at 44 hpi, after the evaluation of their in vitro embryo development, could be used as noninvasive markers of embryo developmental competence and may help to select IVF embryos that would be more suitable for cryopreservation.


Microwave heating in the hydrogen peroxide oxidation of benzene on zeolite catalysts
In this paper benzene hydroxylation with hydrogen peroxide (H2O2) in the presence of the titan-silicates-zeolites was studied. The initial catalyst, HZSM-5 zeolite type was treated to obtain both cobalt- and titan-silicates--zeolite. These improved catalysts were also used for oxidation. To obtain reaction temperature heating was made by conventional techniques and by microwave treatment. From this research it was concluded that reaction temperature is a very important parameter to keep a proper equilibrium between the decomposition rate of hydrogen peroxide and the oxidation rate of aromatic compound. It was also found that microwaves affect the reaction selectivity.


Hostility and aggressive behaviour in first episode psychosis: Results from the OPTiMiSE trial.
The aim of this paper is to determine clinical factors related to hostility and disturbing and aggressive behaviour and to examine the effect of medication on these behaviours in FEP. Data from phase I and II of the OPTiMiSE trial are used. Outcome measures are the hostility item of the Positive and Negative Syndrome Scale (PANSS P7) and the disturbing and aggressive behaviour domain of the Personal and Social Performance scale (PSP-D). Moderate, severe or extreme hostility (PANSS P7 > 3) was present in 42 patients (9.4%). The PANSS P7 and PSP-D were low to moderate but significantly associated with the selected PANSS items: delusions, hallucinatory behaviour, excitement, tension, uncooperativeness, unusual thought content, impulsivity, and lack of judgement and insight. In a subsample of 185 patients (41.5%) with baseline PANSS P7 > 1, the PANSS P7 and PSP-D scores improved in the first 4 weeks of amisulpride treatment. This effect remained significant after controlling for baseline positive symptoms (PANSS P1-P6). No significant differences were found between olanzapine and amisulpride in the second phase of the trial. Clinical risk factors such as poor impulse control, uncooperativeness and excitement could help clinicians in detecting and treating hostile and aggressive behaviour in FEP. Amisulpride could be an effective antipsychotic choice in the treatment of FEP patients who express hostile or aggressive behaviour. Future research is needed to compare the effects of amisulpride and olanzapine on hostility in FEP during the first weeks of treatment.


Chemoselective cycloisomerization of O-alkenylbenzamides via concomitant 1,2-aryl migration/elimination mediated by hypervalent iodine reagents.
As an ambident nucleophile, controlling the reaction selectivities of nitrogen and oxygen atoms in amide moiety is a challenging issue in organic synthesis. Herein, we present a chemodivergent cycloisomerization approach to construct isoquinolinone and iminoisocoumarin skeletons from o-alkenylbenzamide derivatives. The chemo-controllable strategy employed an exclusive 1,2-aryl migration/elimination cascade, enabled by different hypervalent iodine species generated in situ from the reaction of iodosobenzene (PhIO) with MeOH or 2,4,6-tris-isopropylbenzene sulfonic acid. DFT studies revealed that the nitrogen and oxygen atoms of the intermediates in the two reaction systems have different nucleophilicities and thus produce the selectivity of N or O-attack modes.


A new method of creating intervertebral disc disruption of various grades.
The purpose of this study was to develop a model of intervertebral disc disruption capable of (1) internal disruption without excessive disruption to the disc surface, (2) user-defined disruption magnitude and location and (3) interrogation by magnetic resonance imaging. Present models of disc disruption may have some, but not all, of these features. Intravenous tubes were inserted into the intervertebral discs of a cadaveric porcine lumbar spine. Tube placement in the inner annulus was confirmed by magnetic resonance imaging. Each disc was then injected through the intravenous tube with nitrogen gas at pressures of 69 kPa, 172 kPa, 345 kPa and 690 kPa. Before and after injection, edge detection analysis of magnetic resonance imaging images was used to quantify tissue disruption. These values were then multiplied by the thickness of the slices and summed to determine disruption volume for individual discs. Four additional discs were injected with the addition of ink, sectioned and then inspected visually. As the injection pressure increased, the gas volume within the annulus increased significantly as did visualized annular disruption. No significant difference in gas volume was observed between different discs injected with equal pressure. As confirmed by magnetic resonance imaging and dissection, gas volume and tissue disruption within the annulus fibrosus were proportional to the pressure of injected nitrogen. This model of disc disruption promises to provide several advantages in the investigation of disc pathology including (1) user-controlled magnitude of inner annulus disruption, (2) user-controlled tissue disruption localization, (3) minimal disruption of the exterior annulus, (4) independence between the magnitude of external and internal disruption and (5) the ability to visualize resulting disruptions with magnetic resonance imaging.


Maladaptive personality traits and psychopathology in childhood and adolescence: the moderating effect of parenting.
This study examines child and adolescent psychopathology from a maladaptive trait perspective, incorporating both parental and child ratings of parenting as a moderator of the personality-psychopathology association. Hierarchical moderated regression analyses were conducted on a combined sample of referred and nonreferred children and adolescents (N=862, parental ratings of parenting and N=396, child ratings of parenting). The results indicated positive main effects of maladaptive traits on externalizing and internalizing problems, and positive main effects of parental negative control on externalizing problems. Significant interactions were found for Disagreeableness and Emotional Instability with parental Negative Control and for Disagreeableness x Positive Parenting in explaining externalizing problems. The discussion focuses on the contribution of these findings to a better understanding of the trait-psychopathology relationship at young age.


Biodegradation of formaldehyde by a formaldehyde-resistant bacterium isolated from seawater.
A formaldehyde-tolerant bacterium designated as a DM-2 strain was used to biodegrade formaldehyde. The cells, precultivated in the presence of 400 ppm of formaldehyde, were able to degrade formaldehyde in a minimal medium supplemented with up to 400 ppm of formaldehyde in the presence of 3% NaCl. The rate of formaldehyde degradation achieved in this study was 45 ppm/h when the DM-2 culture's optical density at 660 nm was 1.2.


[Primary hemiarthroplasty in proximal humerus fractures].
The surgical treatment of complex proximal humerus fractures is still a great challenge. Not all fracture types can be successfully reconstructed. Indications for a primary joint replacement arise from critical fracture patterns and defined predictors of ischemia in the elderly (age >60 years). If good functional results are to be achieved a soft-tissue-preserving surgical technique, secure tuberosity attachment and accurate soft tissue balancing of the rotator cuff, correct restoration of height, retrotorsion and offset, and appropriate physiotherapy afterwards are essential. In multicentre studies in patients who had undergone primary hemoarthroplasty average Constant-Murlay Scores of 56.0-73.5 point were recorded. At follow-up, 79% of the patients reported only mild pain or none at all, and the ROM was acceptable (41.9% anteversion >90 degrees , 34.7% abduction >90 degrees ). Generally, subjective evaluations were much better than the objective results.The incidence of complications after humeral head replacement is still relatively high, whereas the 10-year survival rate of shoulder hemiarthroplasties has been found in a recent study to be 100%.


Regional cerebellar volumes predict functional outcome in children with cerebellar malformations.
The cerebellum has recently been recognized for its role in high-order functions, including cognition, language, and behavior. Recent studies have also begun to describe a functional topography of the mature cerebellum that includes organization on a mediolateral axis. However, no study to date has examined the relationship between regional cerebellar volume and developmental disabilities in children with cerebellar malformations. The objective of this study was to estimate the extent to which total and regional cerebellar volumes are associated with developmental disabilities in a cohort of children with cerebellar malformations. Children aged 1 to 6 years with a diagnosis of cerebellar malformation underwent standardized outcome measures and quantitative magnetic resonance scanning. The cerebellum was parcellated into seven mediolateral zones (three for each hemisphere plus the vermis) for regional volume analysis. In children with cerebellar malformations, decreased total cerebellar volume was associated with delays in global development, expressive language, cognition, as well as gross and fine motor function. Decreased volume in the right lateral cerebellar hemisphere was related to impaired cognition, expressive language, and gross motor function. Additionally, reduced vermis volume was associated with impaired global development, cognition, expressive language, and gross and fine motor skills, as well as behavior problems and a higher rate of positive autism spectrum screening test. These results begin to define the structural topography of functional outcome in children with cerebellar malformations and should lead to greater accuracy of prognostication as well as timely early developmental interventions.


Comparative transcriptome profiling of virulent and avirulent isolates of Neoparamoeba perurans.
Neoparamoeba perurans, the aetiological agent of amoebic gill disease, remains a persistent threat to Atlantic salmon mariculture operations worldwide. Innovation in methods of AGD control is required yet constrained by a limited understanding of the mechanisms of amoebic gill disease pathogenesis. In the current study, a comparative transcriptome analysis of two N. perurans isolates of contrasting virulence phenotypes is presented using gill-associated, virulent (wild type) isolates, and in vitro cultured, avirulent (clonal) isolates. Differential gene expression analysis identified a total of 21,198 differentially expressed genes between the wild type and clonal isolates, with 5674 of these genes upregulated in wild type N. perurans. Gene set enrichment analysis predicted gene sets enriched in the wild type isolates including, although not limited to, cortical actin cytoskeleton, pseudopodia, phagocytosis, macropinocytic cup, and fatty acid beta-oxidation. Combined, the results from these analyses suggest that upregulated gene expression associated with lipid metabolism, oxidative stress response, protease activity, and cytoskeleton reorganisation is linked to pathogenicity in wild type N. perurans. These findings provide a foundation for future AGD research and the development of novel therapeutic and prophylactic AGD control measures for commercial aquaculture.


Biodiscovery of new Australian thraustochytrids for production of biodiesel and long-chain omega-3 oils.
Heterotrophic growth of thraustochytrids has potential in co-producing a feedstock for biodiesel and long-chain (LC, ≥C(20)) omega-3 oils. Biodiscovery of thraustochytrids from Tasmania (temperate) and Queensland (tropical), Australia, covered a biogeographic range of habitats including fresh, brackish, and marine waters. A total of 36 thraustochytrid strains were isolated and separated into eight chemotaxonomic groups (A-H) based on fatty acid (FA) and sterol composition which clustered closely with four different genera obtained by 18S rDNA molecular identification. Differences in the relative proportions (%FA) of long-chain C(20), C(22), omega-3, and omega-6 polyunsaturated fatty acids (PUFA), including docosahexaenoic acid (DHA), docosapentaenoic acid, arachidonic acid, eicosapentaenoic acid (EPA), and saturated FA, as well as the presence of odd-chain PUFA (OC-PUFA) were the major factors influencing the separation of these groups. OC-PUFA were detected in temperate strains of groups A, B, and C (Schizochytrium and Thraustochytrium). Group D (Ulkenia) had high omega-3 LC-PUFA (53% total fatty acids (TFA)) and EPA up to 11.2% TFA. Strains from groups E and F (Aurantiochytrium) contained DHA levels of 50-61% TFA after 7 days of growth in basal medium at 20 °C. Groups G and H (Aurantiochytrium) strains had high levels of 15:0 (20-30% TFA) and the sum of saturated FA was in the range of 32-51%. β,β-Carotene, canthaxanthin, and astaxanthin were identified in selected strains. Phylogenetic and chemotaxonomic groupings demonstrated similar patterns for the majority of strains. Our results demonstrate the potential of these new Australian thraustochytrids for the production of biodiesel in addition to omega-3 LC-PUFA-rich oils.


Post-induction hypotension with remimazolam versus propofol in patients routinely administered angiotensin axis blockades: a randomized control trial.
Certain routine medication could result in post-induction hypotension (PIH), such as angiotensin axis blockades, which are frequently administered as a first-line therapy against hypertension. Remimazolam is reportedly associated with lesser intraoperative hypotension than propofol. This study compared the overall incidence of PIH following remimazolam or propofol administration in patients managed by angiotensin axis blockades. This single-blind, parallel-group, randomized control trial was conducted in a tertiary university hospital in South Korea. Patients undergoing surgery with general anesthesia were considered for enrollment if the inclusion criteria were met: administration of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, 19 to 65 years old, American Society of Anesthesiologists physical status classification ≤ III, and no involvement in other clinical trials. The primary outcome was the overall incidence of PIH, defined as a mean blood pressure (MBP) < 65 mmHg or decrease by ≥ 30% of the baseline MBP. The time points of measurement were baseline, just before the initial intubation attempt, and 1, 5, 10, and 15 min following intubation. The heart rate, systolic and diastolic blood pressures, and bispectral index were also recorded. Groups P and R included patients administered propofol and remimazolam, respectively, as an induction agent. A total of 81 patients were analyzed, of the 82 randomized patients. PIH was less frequent in group R than group P (62.5% versus 82.9%; t value 4.27, P = 0.04, adjusted odds ratio = 0.32 [95% confidence interval 0.10-0.99]). The decrease in the MBP from baseline was 9.6 mmHg lesser in group R than in group P before the initial intubation attempt (95% confidence interval 3.3-15.9). A similar trend was observed for systolic and diastolic blood pressures. No severe adverse events were observed in either group. Remimazolam results in less frequent PIH than propofol in patients undergoing routine administration of angiotensin axis blockades. This trial was retrospectively registered on Clinical Research Information Service (CRIS), Republic of Korea (KCT0007488). Registration date: 30/06/2022.


Long-term chronic stimulation of internal capsule in poststroke pain and spasticity. Case report, long-term results and review of the literature.
This report describes the long-term follow-up of chronic stimulation of the posterior limb of the internal capsule (IC) adjacent to the sensory thalamus in an elderly patient who suffered pain and spasticity in the left leg due to stroke. Both pain and motor symptoms ameliorated during 5 years of deep brain stimulation. Our case report suggests the possibility to stimulate a more precise representation of the inferior limbs within the IC and thalamus. We propose that chronic stimulation of the IC might be an effective surgical option to motor cortex stimulation when the pain and spasticity are referred to the lower limbs.


Methotrexate intercalated layered double hydroxides with the mediation of surfactants: Mechanism exploration and bioassay study.
Methotrexatum intercalated layered double hydroxides (MTX/LDHs) hybrids were synthesized by the co-precipitation method and three kinds of nonionic surfactants with different hydrocarbon chain lengths were used. The resulting hybrids were then characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM). XRD and FTIR investigations manifest the successful intercalation of MTX anions into the interlayer of LDHs. TEM graphs indicate that the morphology of the hybrids changes with the variation of the chain length of the surfactants, i.e., the particles synthesized using polyethylene glycol (PEG-7) present regular disc morphology with good monodispersity, while samples with the mediation of alkyl polyglycoside (APG-14) are heavily aggregated and samples with the addition of polyvinylpyrrolidone (PVP-10) exhibit irregular branches. Furthermore, the release and bioassay experiments show that monodisperse MTX/LDHs present good controlled-release and are more efficient in the suppression of the tumor cells.


Genome-wide methylation analysis.
The disruption and alteration of genomic methylation patterns is a hallmark of cancer and other disease states. Understanding and characterizing genome-wide methylation will have a profound effect on our understanding of tumorigenesis and provide novel avenues for therapy. This chapter serves to describe techniques that examine genome-wide methylation patterns including luminometric methylation assay, restriction landmark genome scanning, and the cytosine extension assay, which utilize methylation-sensitive restriction enzymes. Additional techniques such as nucleotide separation assays (nearest neighbor analysis and high-performance capillary electrophoresis) and the infinium methylation assay are discussed. These techniques allow for the determination of changes in global methylation levels, as well as regional changes in methylation throughout the genome.


Outcomes and Cost Comparison Between Generic and Conventional Cephalomedullary Nails in the Treatment of Peritrochanteric Femur Fractures.
Although generic orthopaedic implants have been available for several years, there has been slow adoption of this cost-saving option. We hypothesize equivalent outcomes between generic and conventional cephalomedullary nails (CMN) in the treatment of peritrochanteric femur fractures. We evaluated 419 patients undergoing CMN for peritrochanteric femur fracture with a minimum 6-month follow-up. Demographic data, radiographic assessment, and clinical outcomes were compared. Ninety patients were treated with generic implants and 329 patients with conventional implants. The overall complication rate was 7.0%, with a revision surgery rate of 5.4%. No significant differences were seen in demographic variables or surgical factors. Although there was an increased incidence of postoperative infections with conventional nails (P = 0.045), no significant differences were seen in other complications. At our institution, generic nails cost approximately 38% less than their conventional counterparts. There seems to be no increased rate of implant-associated complications with the use of generic CMNs, although allowing for notable cost savings.


Oxygen transfer properties and dimensions of red blood cells in high-altitude camelids, dromedary camel and goat.
To estimate the advantage of the small red blood cells (RBC) of high-altitude camelids for O2 transfer, the kinetics of O2 uptake into and release from the RBC obtained from llama, vicuña and alpaca were investigated at 37 degrees C with a stopped-flow technique. O2 transfer conductance of RBC (G) was estimated from the rate of O2 saturation change and the corresponding O2 pressure difference between medium and hemoglobin. For comparison, O2 kinetics for the RBC of a low-altitude camelid (dromedary camel) and the pygmy goat were determined and previously measured values for human RBC were used. O2 transfer of RBC was found to be strongly influenced by extracellular diffusion, except with O2 release into dithionite solutions of sufficiently high concentration (greater than 30 mM). The G values measured in these 'standard' conditions, Gst (in mmol X min-1 X Torr-1 X (ml RBC)-1) were: high-altitude camelids, 0.58 (averaged for llama, alpaca and vicuña since there were no significant interspecific differences); camel 0.42; goat, 0.42; man, 0.39. The differences can in part be attributed to expected effects of the size and shape of the RBC (volume, surface area, mean thickness), as well as to the intracellular O2 diffusivity which depends on the concentration of cellular hemoglobin. The high Gst of RBC of high-altitude camelids may be considered to enhance O2 transfer in lungs and tissues. But the O2 transfer conductance of blood, theta, equal to Gst multiplied by hematocrit (in mmol X min-1 X Torr-1 X (ml blood)-1), was only slightly higher as compared to other species: 0.20 (llama, alpaca, vicuña), 0.14 (camel), 0.18 (goat), 0.17 (man).


Exercise-induced bronchospasm in children.
This review will encompass definition, history, epidemiology, pathogenesis, diagnosis, and management of exercise -induced bronchospasm in the pediatric individual with and without known asthma. Exercise induced asthma is the conventional term for transient airway narrowing in a known asthma in association with strenuous exercise usually lasting 5-10 minutes with a decline in pulmonary function by at least 10%. Exercise induced asthma will be referred to as exercise induced bronchospasm in an asthmatic. Exercise-induced bronchospasm (EIB ) is the same phenomenon in an individual without known asthma. EIB can be seen in healthy individuals including children as well as defense recruits and competitive or elite athletes. The diagnosis with objective exercise challenge methods in conjunction with history is delineated. Management is characterized with pharmacotherapy and non pharmacotherapeutic measures for underlying asthma as well as exercise induced bronchospasm and inhalant allergy. Children can successfully participate in all sports if asthma is properly managed.


Extensive exchange of rat liver microsomal phospholipids.
Liver microsomal fractions were prepared from rats injected with a single dose of choline [14C]methylchloride or with single or multiple doses of 32Pi. Exchangeability of microsomal phospholipids was determined by incubation with an excess of mitochondria and phospholipid exchange proteins derived from beef heart, beef liver or rat liver. Labeled phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were found to act as a single pool and were 85--95% exchangeable in 1--2h. High latencies of mannose-6-phosphate phosphohydrolase activities and impermeability of microsomes to EDTA proved that phospholipid exchange proteins did not have access to the intracisternal space. If microsomal membranes are largely composed of phospholipid bilayers, the experiments suggest that one or more of the phospholipid classes in microsomal membranes undergo rapid translocation between the inner and outer portions of the bilayer.


Spatio-temporal theta pattern dissimilarity in the right centro-parietal area during memory generalization.
Generalization across past events may guide our action in novel situations. Although generalization is a fundamental memory process, its neural underpinnings are not fully understood yet. In the present experiment, we combinedElectroencephalography(EEG) with multivariate representational similarity analysis (RSA) to examine in particular the role of spatio-temporal patterns of theta oscillations known to be important for associative memory processes, in memory generalization. We recorded EEG while healthy participants (n = 56) performed an acquired equivalence task. In this task, participants first acquired multiple associations among antecedent and consequent stimuli before they were required to transfer the acquired knowledge to novel stimulus pairs, thus probing memory generalization. Our behavioural data indicated that participants learned the initial associations well and transferred these associations successfully to novel test stimuli, demonstrating successful memory generalization. Our neural data revealed that, compared to mere memory retrieval, generalization was associated with significantly increased pattern dissimilarity of theta activity in the right centro-parietal area (electrodes P4 and P6). This pattern was specific to theta oscillations and not observed in other frequency bands. Our findings suggest an important role of theta oscillations in memory generalization, potentially serving the reactivation and integration of distinct events that enable the generalization across experiences.


Free radical reaction and biological defense mechanism in the pathogenesis of prolonged vasospasm in experimental subarachnoid hemorrhage.
The relationship between free radical reactions and the defense mechanisms against them was investigated in the pathogenesis of prolonged vasospasm following experimental subarachnoid hemorrhage (SAH) in dogs. The concentration of lipid peroxides in the cerebro spinal fluid (CSF) increased markedly up to the eighth day following SAH; the concentrations also rose in the arterial wall (p less than 0.01) and the gray matter of the temporal lobe where the subarachnoid blood clots were (p less than 0.01). On the other hand, the activity of superoxide dismutase (SOD) decreased significantly up to the eighth day after SAH (p less than 0.01), and there was a gradual increase of glutathione peroxidase (GSH-px) in the CSF. In the arterial wall, there was a slight decrease in the activity of SOD, a significant decrease in the activity of GSH-px (p less than 0.01), and also a significant decrease in the concentration of glutathione (p less than 0.01) up to the eighth day following SAH. In conclusion, lipid peroxidation with insufficient biological defense mechanisms against it in the arterial wall, concomitant with that in the CSF, might take part in the genesis of prolonged vasospasm following SAH.


The Escherichia coli adenylate cyclase complex. Stimulation by potassium and phosphate.
In Escherichia coli, adenylate cyclase activity in toluene-treated cells can be inhibited by glucose while the activity in a broken cell preparation cannot. Adenylate cyclase activity in the permeabilized but not in broken cells is stimulated somewhat specifically and additively by potassium and phosphate. Kinetic studies show sigmoid substrate-velocity curves for the toluene-treated cells but hyperbolic curves for the broken cells. The stimulatory effects of potassium and phosphate on adenylate cyclase activity in tolulene-treated cells are associated with increases in the Vmax and Km for ATP. While the enzyme activity in toluene-treated cells shows a preference for magnesium over manganese, the reverse is observed in broken cells. Stimulation of adenylate cyclase activity in toluene-treated cells requires the presence of the proteins of the phosphoenolpyruvate:sugar phosphotransferase system (PTS). The PTS proteins can be phosphorylated in a P-enolpyruvate-dependent reaction. The stimulatory effects of ions will not occur if the PTS proteins are not phosphorylated. Since potassium phosphate stimulates both adenylate cyclase and PTS activities in toluene-treated cells, it is proposed that the effect of potassium phosphate on adenylate cyclase activity is mediated through an effect on the PTS. A model for dual regulation by glucose of adenylate cyclase activity is proposed. This model involves regulation of both the condition of the PTS proteins as well as the cellular concentration of phosphate.


Molecular detection of Imbrasia belina proteins associated with allergic reactions on harvesters and consumers from selected districts in Matabeleland: a comparative study.
Harvesting and consuming insects (entomophagy), particularly Imbrasia belina is widespread in developing countries like Zimbabwe. Due to their extraordinary nutritional content, tastiness, ease of processing and storage, Imbrasia belina has become a delicacy, reachable nutritious complement, and money source for some people in Zimbabwean communities. However, some harvesters and consumers have become allergic to the Imbrasia belina, popularly known as Mopani worms. This has been attributed or associated with the changes in the genetic structure of Imbrasia belina. Therefore, this research sought to compare the presence of the genes associated with allergic reactions to mopane worms from Gwanda and Umguza districts in Zimbabwe. A lab-based observational study was conducted on collected Imbrasia belina samples from both districts. Fifteen samples of mopane worms were collected from each district, and DNA extraction was performed using DNeasy blood and tissue kit. The DNA extraction products were then amplified using a Polymerase chain reaction. The polymerase chain reaction products were run on agarose gel electrophoresis to determine the presence of the target genes. Three of the five samples from Gwanda district were positive for the tropomyosin gene, whereas two samples from Umguza district were positive. All the samples from the two districts were negative for arginine kinase genes. The study results highlighted that allergic reactions to Imbrasia belina reported in Gwanda district are associated with the presence of the tropomyosin gene, which has undergone polymorphism. Responsible authorities such as Gwanda local authority should develop bylaws that govern Imbrasia belina harvesting in the district.


The effects of age and gender on the pharmacokinetics of irbesartan.
Single dose pharmacokinetics and safety of irbesartan, an angiotensin II receptor antagonist, were evaluated in healthy young and elderly male and female subjects. Irbesartan was administered as two 25 mg capsules after a 10 h fast to 12 young men, 12 young women, 12 elderly men and 12 elderly women. Serial blood and urine sample were collected up to 96 h after the dose. Plasma and urine samples were analysed for irbesartan by h.p.l.c./fluorescence methods. No statistically significant gender effects were observed in peak plasma concentration (Cmax), area under the curve (AUC), and terminal elimination half-life (t1/2) of irbesartan. The geometric mean AUC and Cmax increased by about 43% and 49%, respectively, in the elderly subjects. Also the time to peak was significantly shorter in the elderly subjects compared with that observed in the young subjects. Renal clearance ofirbesartan was significantly reduced in the elderly females but this reduction is not likely to be of any clinical relevance since less than 3% of the administered dose of irbesartan is excreted unchanged in the urine. Although there was an effect of age on the pharmacokinetics of irbesartan, based on the safety and efficacy profile, no adjustment in irbesartan dosage is necessary with respect to age or gender.


Odd and Even Numbered Ferric Wheels.
The structurally related odd and even numbered wheels [FeIII 11 ZnII 4 (tea)10 (teaH)1 (OMe)Cl8 ] (1) and [FeIII 12 ZnII 4 (tea)12 Cl8 ] (2) can be synthesized under ambient conditions by reacting FeIII and ZnII salts with triethanolamine (teaH3 ), the change in nuclearity being dictated by the solvents employed. An antiferromagnetic exchange between nearest neighbors, J = -10.0 cm-1 for 1 and J = -12.0 cm-1 for 2, leads to a frustrated S = 1/2 ground state in the former and an S = 0 ground state in the latter.


Molecular evolution and phylogenetic analysis of genes related to cotton fibers development from wild and domesticated cotton species in Gossypium.
The domestication of both diploid and tetraploid cotton species was carried out for fiber utilization. To understand the origin and domestication of fibers, 18 genes related to fiber development were individually cloned and sequenced from 22 different cotton species. Their structures, phylogenetic relationship and molecular evolution were further studied. In the orthologous and homeologous loci of the 18 genes, the sequence and structure of 72.22% were conserved and 27.78% were diverse. Tree topologies constructed based on the combined sequences showed that all 13 D-genome species were congruent with Fryxell's subsection taxonomy, the A- and D-subgenomes independently evolved in the allopolyploid after polyploid formation, and Gossypium raimondii had the closest relationship with all allotetraploids of D-subgenomes. The molecular evolutionary rates revealed approximately equivalent rates among different D-genome species, and purifying selection acted on all genes in the wild D-genome species. Among orthologs and homeologs, the D-subgenomes had higher evolutionary rates than the A-subgenomes in tetraploid cotton species, and the cultivars had higher evolutionary rates than either the semi-domesticated or wild species. Our study revealed that human domestication altered the molecular evolutionary pattern of genes related to fiber development, and Gossypium hirsutum endured greater selective pressures than Gossypium barbadense during the domestication process.


Can the binding of GABA, glycine and beta-alanine to synaptic receptors be determined in the presence of a physiological concentration of Na+?
Bicuculline- and strychnine-sensitive components of the binding of GABA, glycine and beta-alanine, which can be demonstrated in the presence of a physiological concentration of Na+, might be related to synaptic receptors.


Use of urine alarms in toilet training children with intellectual and developmental disabilities: A review.
The purpose of this review is to describe and evaluate the existing research on the use of urine alarms in the daytime toilet training of children with intellectual and developmental disabilities (IDD). A systematic literature search yielded 12 studies, many of which were published over a decade ago. The findings suggest that interventions that incorporate the use of urine alarms are promising in the treatment of daytime enuresis for children with IDD; however, more carefully controlled research is needed to confirm these findings and elucidate the precise role urine alarms may play in toileting interventions. Methodological strengths and limitations of the body of research are discussed.


Control of Salmonella enteritidis in Sweden.
The Swedish control of Salmonella, with special reference to Salmonella enteritidis, in poultry is described. The control is directed at all serotypes of Salmonella and imported grandparent chickens are controlled, which is considered to be the main reason why Sweden so far is not found to be involved in the worldwide spread of different phagetypes of S. enteritidis. However, this spread has initiated a more stringent control of Salmonella in layers as earlier existed in broilers. Since 1990, 90% of the layer flocks are voluntarily tested for Salmonella before slaughter by bacteriological examination of pooled faecal samples. If S. enteritidis is isolated the flock is destroyed. This test, and in addition two similar tests during the production are mandatory as of January 1st, 1994. The voluntary Salmonella control programme has also been extended to all of the layer parents and hatcheries since 1991. Only heat-treated feed is given to all layer chickens during the rearing period and its use is becoming gradually more common also during the production period. Since 1987, four layer flocks have been found to be infected by S. enteritidis phagetype 4 and one flock with phagetype 6. During 1970-1984, 90% of all flocks of broilers were voluntarily tested bacteriologically for Salmonella before slaughter, and since 1984 such a control is mandatory to all flocks. As a result of this and other controls, S. enteritidis has not been isolated from broilers since 1972. Based on a governmental regulation from 1961, introduced as a result of a large Salmonella epidemic in 1953, Sweden runs an active, official control of Salmonella (Wierup et al., 1992).(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiology of vestibular schwannoma in the United States, 2004-2016.
Vestibular schwannomas (VS) are nonmalignant tumors of the eighth cranial nerve and are the most common nonmalignant nerve sheath tumor. This study provides the most comprehensive and current analysis of VS epidemiology in the United States. Incidence data were obtained from the Central Brain Tumor Registry of the United States, from 2004 to 2016 for VS. Age-adjusted incidence rates (AAIRs), rate ratios (AAIRRs), and prevalence ratios (AAPRs) per 100 000 were analyzed by age, sex, race and ethnicity, and laterality. Additional analyses were performed to assess differences in treatment, laterality, and diagnostic confirmation. Incidence of VS was highest among adults (aged 65-74 years, AAIR: 3.18, 95% confidence interval [CI]: 3.15-3.25). However, there was a much higher distribution of bilateral tumors compared to unilateral in children aged 0-19 years (28.5% vs 1.0%, P < .001). VS incidence was highest among white non-Hispanics (AAIR:1.30, 95% CI: 1.29-1. 31) and lowest among black non-Hispanics. Incidence of radiographically confirmed VS increased from 2004 to 2016 (annual percent change: 1.64, 95% CI: 0.15-3.16, P = .03). For treatment, 40.1% received surgery, while only 23.7% received radiation. There were an estimated 44 762 prevalent cases of VS in 2016 (AAPR: 12.17, 95% CI: 12.06-12.29). VS incidence and prevalence are highest among adults and white non-Hispanics. Bilateral VS was more common among children. There was an increase of radiographically confirmed VS over time. A higher proportion of patients received surgical treatment than radiotherapy. Population-based statistics provide healthcare professionals with vital information regarding disease burden and help improve patient care.


Hematopoietic stem cell transplantation for Morquio A syndrome.
Morquio A syndrome features systemic skeletal dysplasia. To date, there has been no curative therapy for this skeletal dysplasia. No systemic report on a long-term effect of hematopoietic stem cell transplantation (HSCT) for Morquio A has been described. We conducted HSCT for 4 cases with Morquio A (age at HSCT: 4-15years, mean 10.5years) and followed them at least 10years (range 11-28years; mean 19years). Current age ranged between 25 and 36years of age (mean 29.5years). All cases had a successful full engraftment of allogeneic bone marrow transplantation without serious GVHD. Transplanted bone marrow derived from HLA-identical siblings (three cases) or HLA-identical unrelated donor. The levels of the enzyme activity in the recipient's lymphocytes reached the levels of donors' enzyme activities within two years after HSCT. For the successive over 10years post-BMT, GALNS activity in lymphocytes was maintained at the same level as the donors. Except one case who had osteotomy in both legs one year later post BMT, other three cases had no orthopedic surgical intervention. All cases remained ambulatory, and three of them could walk over 400m. Activity of daily living (ADL) in patients with HSCT was better than untreated patients. The patient who underwent HSCT at four years of age showed the best ADL score. In conclusion, the long-term study of HSCT has demonstrated therapeutic effect in amelioration of progression of the disease in respiratory function, ADL, and biochemical findings, suggesting that HSCT is a therapeutic option for patients with Morquio A.


Stereotactic ablative radiation for pancreatic cancer on a 1.5 Telsa magnetic resonance-linac system.
Ablative radiation therapy (A-RT) appears to improve outcomes in locally advanced pancreatic cancer (LAPC) yet requires solutions for respiratory and digestive motion. We report outcomes of A-RT for pancreatic cancer using 1.5 T MR-adaptive treatment delivery. Between March 2020 and July 2021, we treated 30 patients with pancreatic cancer with 50 Gy in 5 fractions (biologically effective dose [BED10] = 100 Gy10) using a novel compression belt workflow and remote planning on the Unity 1.5 T MR linac system. Cumulative incidence of progression was computed from A-RT initiation with death as a competing risk. Overall (OS) and progression-free survival (PFS) were calculated using Kaplan Meier methods. Of 30 patients, most (73 %) were locally advanced, 4 (13 %) were metastatic, 2 (7 %) were medically inoperable, and 2 (7 %) were locally recurrent. Most (73 %) received FOLFIRINOX prior to A-RT. Median follow-up times from diagnosis and A-RT were 17.6 (IQR 15.8-23.1) and 11.5 months (IQR 9.7-16.1), respectively. Cumulative incidences at 1-year of local and distant progression were 19.3 % (95 %CI 6.7-36.8 %) and 47.4 % (95 %CI 26.7-65.6 %), respectively. Median OS from diagnosis and A-RT were not reached. One-year OS from diagnosis and A-RT were 96.4 % (95 %CI 77.2-99.5 %) and 80.0 % (95 %CI 57.3-91.4 %), respectively. Median and 1-year PFS were 10.1 months (95 %CI 4.4-14.4) and 39.7 % (95 %CI 20.3-58.5 %), respectively. No grade 3 + toxicities were observed. A-RT using the 1.5 T Unity MR Linac resulted in promising LC and OS with no severe toxicity in patients with LAPC despite radiosensitive organs adjacent to the target volumes. Longer follow-up is needed to assess long-term outcomes.


Surgical resection for non-familial adenomatous polyposis-related intra-abdominal fibromatosis.
Intra-abdominal fibromatosis (IAF) in the context of familial adenomatosis polyposis (FAP) is associated with significant morbidity and high recurrence rates after surgical resection. Non-surgical treatments are therefore advocated. This study explored outcomes in patients with IAF not associated with FAP who underwent surgical resection. Data were analysed from a prospectively collected database at a sarcoma tertiary referral centre. From 2001 to 2011, 15 patients without FAP underwent primary curative surgical resection of IAF. Their median (range) age was 42 (19-64) years. Median tumour size was 18 (8.5-25) cm and weight 1306 (236-2228) g. Complete macroscopic clearance was obtained in all patients. There were no deaths in hospital or within 30 days and only one patient developed a major complication. Median follow-up was 40 (6-119) months. During follow-up two patients developed a recurrence after a disease-free interval of 12 and 16 months. In contrast to FAP-associated IAF, non-FAP-associated IAF has a very low recurrence rate after surgical resection. Surgical resection is therefore advocated as first-line treatment in patients with non-FAP-associated IAF when resection can be performed with low morbidity.


Doxorubicin-anti-carcinoembryonic antigen immunoconjugate activity in vitro.
An in vitro model consisting of a series of 11 human cancer cell lines with varying density of expression of membrane carcinoembryonic antigen (CEA) has been used to evaluate conjugates of doxorubicin (Adriamycin) covalently linked by a carbodiimide method to goat polyclonal antibodies and mouse monoclonal antibodies to CEA. Conjugates were produced which retained both antigen binding and drug cytotoxicity. IC50 values were determined for free drug, free drug mixed with unconjugated antibodies and for the immunoconjugates. Cell lines that were very sensitive to free drug (IC50 less than 100 ng/ml) were also found to be highly sensitive to conjugated drug and similarly cell lines resistant to drug (IC50 greater than 1,000 ng/ml) were also resistant to conjugated drug. Although there was no correlation between CEA expression and conjugates efficacy, competitive inhibition studies using autologous antibody to block conjugate binding to cells indicated immunoconjugates specificity for the CEA target.


The effect of Neurolinguistic Programming practices on organizational citizenship behaviour of nurses: A randomized controlled study.
The aim of this study is to evaluate the effect of Neurolinguistic Programming practices on organizational citizenship behavior in nursing. Neurolinguistic Programming practices are used for different purposes in many areas, and they can also be used to contribute to the acquisition of organizational citizenship behaviour. The research is a randomized controlled trial. The sample of the study consisted of 180 nurses. The data of the study were collected through structured face-to-face interviews conducted with the nurses in the sample group, Neurolinguistic Programming training group, standard training and control groups between January and April 2020 after Neurolinguistic Programming training was received by the researcher. The Chi-squared test and the analysis of variance (ANOVA) were used to analyze the collected data. A statistically significant difference was found in the total score of the organizational citizenship behaviour in the Neurolinguistic Programming training group compared with the standard training group and the control group (p < .05). The use of Neurolinguistic Programming practices can be an effective method for nurses to gain organizational citizenship behaviour. Neurolinguistic Programming practices can be used to achieve the desired goals, especially for the acquisition of informing and participation, tolerance and conscientiousness behaviours. Organizational citizenship behaviour exhibited by employees is very important for organisations. With this behaviour, nurses can improve all processes, from the quality of care services they provide to patients, to satisfaction. Findings of this study may be used to increase work satisfaction of nurses and to improve the quality of services received by patients.


Effects of a long-term exposure with OTA or OTC on functions of a human monocytic cell line.
An in-vitro model was developed to study the effects of a long-term exposure with a low concentration of ochratoxin A (OTA) or ochratoxin C (OTC) on a human monocytic cell line (THP-1).Cells were propagated in 24-well cell culture plates for 15 days. OTA and OTC preparations, respectively, at a concentration of 1 ng/ml were included in the cell culture medium during the whole cultivation period. At the end of the exposure time, parameters of cell viability and cell function were examined.After 15 days of exposure to ochratoxins, viability and function of the THP-1 cell line were modulated. Mitochondrial activity and the production of IL-6 were increased by all mycotoxin preparations. Cell membrane integrity was disturbed, proliferation and the production of TNF-α and IL-8 were inhibited. These parameters were most severely affected by mycotoxin preparations containing OTC.Our results show that long term exposure to OTA and especially OTC in low concentrations can cause subtle alterations of cell viability and function which may have remarkable consequences for human and animal health. In this context it seems to be necessary to study the contamination of food and feed stuffs with OTC more intensively.


Reevaluation of the BRCA2 truncating allele c.9976A > T (p.Lys3326Ter) in a familial breast cancer context.
The breast cancer predisposition gene, BRCA2, has a large number of genetic variants of unknown effect. The variant rs11571833, an A > T transversion in the final exon of the gene that leads to the creation of a stop codon 93 amino acids early (K3326*), is reported as a neutral polymorphism but there is some evidence to suggest an association with an increased risk of breast cancer. We assessed whether this variant was enriched in a cohort of breast cancer cases ascertained through familial cancer clinics compared to population-based non-cancer controls using a targeted sequencing approach. We identified the variant in 66/2634 (2.5%) cases and 33/1996 (1.65%) controls, indicating an enrichment in the breast cancer cases (p = 0.047, OR 1.53, 95% CI 1.00-2.34). This data is consistent with recent iCOGs data suggesting that this variant is not neutral with respect to breast cancer risk. rs11571833 may need to be included in SNP panels for evaluating breast cancer risk.


Bench-to-bedside review: Mitochondrial injury, oxidative stress and apoptosis--there is nothing more practical than a good theory.
Apoptosis contributes to cell death in common intensive care unit disorders such as traumatic brain injury and sepsis. Recent evidence suggests that this form of cell death is both clinically relevant and a potential therapeutic target in critical illness. Mitochondrial reactive oxygen species (ROS) have become a target for drug discovery in recent years since their production is characteristic of early stages of apoptosis. Among many antioxidant agents, stable nitroxide radicals targeted to mitochondria have attracted attention due to their ability to combine electron and free radical scavenging action with recycling capacities. Specific mechanisms of enhanced ROS generation in mitochondria and their translation into apoptotic signals are not well understood. This review focuses on several contemporary aspects of oxidative stress-mediated mitochondrial injury, particularly as they relate to oxidation of lipids and their specific signaling roles in apoptosis and phagocytosis of apoptotic cells.


[Nasal route flexible broncho-fiberscopy, as a tool of mass examination for hilar type lung cancer (author's transl)].
Early detection of lung cancer is mandatory problem in the medical field. Although, chest x-p examination is a strong armament for detection of peripheral type of lung cancer, the method has rather weak point in detection of hilar type of bronchogenic carcinoma. Bronchoscopy is essential method for diagnosis of bronchial changes of this disease. It is, however, not popular method yet, because of its troublesome technique, such as insertion of tracheal tube, eventhough new instrument of flexible fiber bronchoscopy makes us very much easy way to use, compared with old-fashioned rigid bronchoscopy. For mass examination of high risk group of bronchogenic carcinoma (chromate workers), we are using nasal route flexible fiberbronchoscopy. Comparing of this method with previously used trans-oral route, both easiness of the technique on doctor's side, and comfort during the examination on the patients's side revealed favorable results for nasal method.