Value of the brain angioscintigraphy in posterior view.
The results obtained with intravenous brain angioscintigraphy (IBAS) with 99 mTc-DTPA(Sn) are evaluated in 61 patients with clinical suspicion of cerebellar, cerebral or cranial lesions of posterior location or without focal signs or with a previous IBAS in anterior view being normal or of low significance. One hundred patients without demonstrable cerebral or cranial pathology were explored to define the normal characteristics and variation of the IBAS in posteior view. Of the 61 patients with pathology, 45 showed angioscintigraphic alterations. The following angioscintigraphic patterns were found: 1. Perfusion increased, 2. Perfusion diminished, 3. Flip-flop, 4. Mixed pattern, 5. Circulatory arrest, 6. Jugular venous reflux, 7. Normal IBAS associated with an abnormal morphologicall study, 8. Normal IBAS associated with a normal morphological study.


Genetic determination of diabetes mellitus in patients with cystic fibrosis. Multicenter Cystic Fibrosis Study Group.
Data from 1348 patients with cystic fibrosis in mid-Europe show that the prevalence of diabetes mellitus in these patients is 4.9%, that diabetes develops in more female than male patients with cystic fibrosis during childhood and adolescence and at a younger age, and that diabetes mellitus is more likely to affect delta F508 homozygous patients.


Microbial transformations of labelled nitrogen in a clear-cut pine plantation.
Labelled nitrogen was used to evaluate the effects of intensive forest management on soil nitrogen transformations. The total release of N into inorganic forms (ammonium plus nitrate) was much greater than net N mineralization in all treatments. Immobilization of N by microbes was greatest in minimally-treated harvested plots, while the turnover of N within soil microbes was greatest in intensively-treated plots. Ammonium was immobilized 2.4-3.2 times more rapidly than nitrate in havested plots; nitrification in disturbed sites could thus increase the availability of N to regrowing vegetation.


Uptake, depuration, dose estimation and effects in zebrafish exposed to Am-241 via dietary route.
Zebrafish were chronically exposed to Am-241, an alpha-emitting radionuclide via daily consumption of an enriched artificial diet. Am-241 uptake was quantified in Danio rerio after 5 and 21 days of exposure via daily Am-spiked food ingestion and after 21 days of exposure followed by 5 days of depuration. Americium accumulates mostly in digestive tract, muscle, rest of the body but the accumulation levels and trophic transfer rate (0.033-0.013%) were low. Corresponding cumulative doses were calculated for the whole body (9 mGy) and for the digestive tract (42 mGy) with internal alpha radiation contributing to more than 99% of the total dose. Genotoxic effects (gamma-H2AX assay) and differential gene expressions of main biological functions were examined. Although fish were exposed to a low dose rate of 13 μGy h-1, DNA integrity and gene expression linked to oxidative stress, hormonal signaling and spermatogenesis were altered after 21 days of Am-241 exposure. These results underline the higher toxicity of alpha emitter Am-241, as compared to other studies on gamma radiation exposure.


A comparison of vision-related quality of life between Defocus Incorporated Soft Contact (DISC) lenses and single-vision spectacles in Chinese children.
This study aimed to compare the vision-related quality of life (VRQoL) between Defocus Incorporated Soft Contact (DISC) lenses and single-vision spectacles in Chinese children, in order to evaluate their visual performance and subjective acceptance of this bifocal designed contact lenses treatment. Chinese participants aged 7 to 12 years, with myopia of -4.00 to -0.75 D, astigmatism < 1.50 D, and monocular best-corrected visual acuity 0.0 or better, were recruited in the study. All participants had been wearing DISC lenses, or single-vision spectacles, for the last 6 to 18 months and were requested to complete the routine ocular examination and Chinese version of the Pediatric Refractive Error Profile (PREP 2) questionnaire. The questionnaire consisted of 7 scales: vision, symptoms, appearance, activities, handling, peer perception, and overall score. According to their habitual correction modalities, fifty-four children were allocated to the DISC group and 56 to the single-vision spectacles group. A generalized linear model was fitted to assess variables associated with the PREP 2 score. Participants wearing DISC lenses scored significantly higher than those wearing single-vision spectacles for vision, appearance, activities, peer perception, and overall (all P < 0.05). The improvement of VRQoL in the DISC group was mainly represented in appearance, peer perception, and activities. The quality of life improved more for older participants on scales of vision, symptoms, handling, appearance, and overall score (all P < 0.05). The interaction between treatment and age was statistically significant for the activities scale (P < 0.05). DISC lens wear significantly improves VRQoL in Chinese children compared with single-vision spectacles for most of the survey scales, especially in the areas of appearance, peer perception, and activities. The benefits provided by DISC lenses contribute to greater satisfaction than single-vision spectacles for myopic children.


The effect of epostane, a 3-beta hydroxy steroid dehydrogenase inhibitor, on maternal and fetal steroid levels during mid-gestation.
A double-blind, placebo-controlled trial was conducted to assess the maternal and fetal endocrine effects of epostane, an inhibitor of progesterone synthesis, in mid-pregnancy. Although present in the maternal circulation, epostane was not detected in cord blood or amniotic fluid. Maternal and fetal progesterone levels fell by 80% and 95% respectively with maintenance of the fetal arterio-venous difference while oestradiol and aldosterone levels were affected to a lesser extent. The mechanism of 3-beta hydroxy steroid dehydrogenase suppression and the relation between fetal and maternal progesterone levels are discussed.


Attitudes of Kuwaiti parents toward physical punishment of children.
The major aim was to describe parental attitudes to physical punishments and examine their sociodemographic correlates. A related aim was to assess the association of parents' own experience of physical punishment with attitudes to punishment of children. A cross-sectional survey was conducted during the second week of December, 1996 in five general clinics covering the major administrative areas of Kuwait: 337 Kuwaiti mothers and fathers with at least one living child were contacted; 95% were successfully interviewed using a structured questionnaire. Eighty-six percent of parents agreed with physical punishment as a means of child disciplining. Agreement with punishment was higher in case of serious misbehaviors such as stealing (63%), sniffing glue and using drugs (77%). Multiple regression results showed that parent's lower level of education and Bedouin ethnicity were positively associated with agreement on physical punishment. Larger percentages of parents who had experienced physical punishments themselves agreed with such punishment to discipline their children, but this was not statistically significant. In recent years education has become widespread for both sexes. An inverse association between educational level and agreement on physical beating suggest that attitudes to this form of child disciplining are changing. Those with a Bedouin ethnic background still adhere more strictly to the traditional forms of child disciplining including physical beating. There is a need for conducting research on the possible negative psychosocial impacts of physical punishment in view of findings from other countries.


An Observational Cohort Study to Evaluate the Impact of a Tailored Medicines Optimisation Service on Medication Use, Accident and Emergency Department Visits, and Admissions Among Patients Identified with Medication Support Needs in Secondary Care.
Quantifying the impact of pharmacy interventions, such as tailored medicines optimisation, can be challenging owing to the sometimes-indirect nature of their effect on patient outcomes such A&E (Accident & Emergency) attendance, hospital admission and length of stay. This study aimed to assess the impact of the, Lewisham Integrated Medicines Optimisation Service (LIMOS) on medicines self-management, A&E attendances and hospital admissions. The study was conducted as a retrospective and prospective observational evaluation of patients referred to LIMOS at University Hospital Lewisham between April and September 2016. Only patients with an appropriate referral that received a LIMOS intervention within the study period were considered eligible. The main outcomes examined pre- and post-LIMOS included medicines self-management, A&E attendance, number of admissions, as well as length of stay. Data were collected for a total of 193 patients. Over half (56.4%, n = 109) identified as female with a mean age of 78 years at the time of referral. The number of hospital admissions decreased significantly post-LIMOS (-0.36 ± 1.87, 95% CI -0.63-0.10). Furthermore, the mean reduction in length of stay was significant and decreased by over a week (19.58 vs 11.09 days post-LIMOS, -7.67 ± 48.57, 95% CI -14.57--0.78). There was a significant increase in A&E visits observed post-intervention (0.78 ± 1.93, 95% CI 0.50-1.06); however, the majority (63%, n =165/261) occurred over 90 days post-intervention. There was a significant reduction in the number of patients self-managing medication post-LIMOS, with the number of patients receiving additional support with their medication increasing (-0.38 ± 0.50, 95% CI -0.45--0.31). LIMOS, therefore, successfully identified patients who were unable to manage their medicines. Specialist pharmacy interventions, which include support with medicines management, have a positive impact on admission avoidance and length of hospital stay.


Angiotensin-converting enzyme: serum levels during normal pregnancy.
ACE activity of the serum of 52 normal pregnant women was measured in vitro under conditions of substrate saturation with Hip-His-Leu as substrate. The product His-Leu was measured by fluorimetry after reaction with o-phthaldehyde. ACE activity (nmol/min/ml serum) was 30.6 +/- 7.8, 28.8 +/- 7.4, and 30.9 +/- 8.2 for the first, second, and third trimester of pregnancy, respectively. No statistically significant differences (p greater than 0.05) in ACE activity were detected among the three trimesters of normal pregnancy with either serum volume or serum protein as reference value. These values are within the range reported by Friedland and Silverstein13 for 51 male and seven female healthy blood bank donors. We conclude that the evolution of normal pregnancy does not significantly modify the levels of ACE in peripheral blood serum.


[Microsurgical treatment of lesions of the proximal segment of the oviduct. Isthmo-ostial reimplantation. Isthmo-ostial anastomosis and isthmo-uterine reimplantation].
The authors, who operated on 187 patients with 277 interstitial sections of the isthmus, describe their microsurgical techniques for isthmo-ostial anastomosis, for isthmo-ostial reimplantation and for isthmo-uterine reimplantation. Histological analysis of the lesions and the anatomical features of the proximal segment of the tube justify their method. Patency is re-established and the results are encouraging. All the same, these partial proximal lesions can be markedly improved with success by medical treatment before operation.


Anatomy of the retrohepatic tunnel in a Chinese population and its clinical application in liver surgery.
Liver hanging maneuver (LHM) is an important technique in liver surgery. However, applied anatomy of the retrohepatic tunnel for the surgical approach in Chinese population needs further study. In this study, to explore the basic anatomy of retrohepatic tunnel and its clinical application in a Chinese population, a total of 32 formalin-fixed cadavers were dissected, related parameters were measured, and their clinical applications were discussed. The length of the retrohepatic tunnel was (60.6 ± 9.9) mm. The width of the retrohepatic tunnel superior opening was (13.8 ± 3.9) mm. The width of the retrohepatic tunnel inferior opening was (15.2 ± 7.4) mm. The hepatic short vessels were distributed along the middle and lower 1/3 of hepatic inferior vena cava (HIVC), with a slight predominance on its left wall. A few hepatic short vessels were distributed along the upper 1/3 of the HIVC. We concluded: the anatomy of the retrohepatic tunnel provides a basis for use of LHM in liver surgery; more hepatic short vessels from hepatic caudate lobe can be preserved via right approach. The retrohepatic tunnel can be used as a good surgical approach in liver surgery; its application also has important significance in laparoscopic minimally invasive liver surgery.


Age and vocabulary knowledge differentially influence the N400 and theta responses during semantic retrieval.
Using electroencephalography (EEG) to study the neural oscillations supporting language development is increasingly common; however, a clear understanding of the relationship between neural oscillations and traditional Event Related Potentials (ERPs) is needed to disentangle how maturation of language-related neural networks supports semantic processing throughout grade school. Theta and the N400 are both thought to index semantic retrieval but, in adults, are only weakly correlated with one another indicating they may measure somewhat unique aspects of retrieval. Here, we studied the relationship between the N400 amplitude and theta power during semantic retrieval with key indicators of language abilities including age, vocabulary, reading comprehension and phonological memory in 226 children ages 8-15 years. The N400 and theta responses were positively correlated over posterior areas, but negatively correlated over frontal areas. When controlling for the N400 amplitude, the amplitude of the theta response was predicted by age, but not by language measures. On the other hand, when controlling theta amplitude, the amplitude of the N400 was predicted by both vocabulary knowledge and age. These findings indicate that while there is a clear relationship between the N400 and theta responses, they may each index unique aspects of development related to semantic retrieval.


An Easy and Economical Way to Produce a Three-Dimensional Bone Phantom in a Dog with Antebrachial Deformities.
3-D surgical planning for restorative osteotomy is costly and time-consuming because surgeons need to be helped from commercial companies to get 3-D printed bones. However, practitioners can save time and keep the cost to a minimum by utilizing free software and establishing their 3-D printers locally. Surgical planning for the corrective osteotomy of antebrachial growth deformities (AGD) is challenging for several reasons (the nature of the biapical or multiapical conformational abnormalities and lack of a reference value for the specific breed). Pre-operative planning challenges include: a definite description of the position of the center of rotation of angulation (CORA) and proper positioning of the osteotomies applicable to the CORA. In the present study, we demonstrated an accurate and reproducible bone-cutting technique using patient-specific instrumentations (PSI) 3-D technology. The results of the location precision showed that, by using PSIs, the surgeons were able to accurately replicate preoperative resection planning. PSI results also indicate that PSI technology provides a smaller standard deviation than the freehand method. PSI technology performed in the distal radial angular deformity may provide good cutting accuracy. In conclusion, the PSI technology may improve bone-cutting accuracy during corrective osteotomy by providing clinically acceptable margins.


Potentiometric determination of trypsin using a polymeric membrane polycation-sensitive electrode based on current-controlled reagent delivery.
A potentiometric biosensor for the determination of trypsin is described based on current-controlled reagent delivery. A polymeric membrane protamine-sensitive electrode with dinonylnaphthalene sulfonate as cation exchanger is used for in situ generation of protamine. Diffusion of protamine across the polymeric membrane can be controlled precisely by applying an external current. The hydrolysis catalyzed with trypsin in sample solution decreases the concentration of free protamine released at the sample-membrane interface and facilitates the stripping of protamine out of the membrane surface via the ion-exchange process with sodium ions from the sample solution, thus decreasing the membrane potential, by which the protease can be sensed potentiometrically. The influences of anodic current amplitude, current pulse duration and protamine concentration in the inner filling solution on the membrane potential response have been studied. Under optimum conditions, the proposed protamine-sensitive electrode is useful for continuous and reversible detection of trypsin over the concentration range of 0.5-5UmL(-1) with a detection limit of 0.3UmL(-1). The proposed detection strategy provides a rapid and reagentless way for the detection of protease activities and offers great potential in the homogeneous immunoassays using proteases as labels.


[Thyroid gland ultrasound screening (Papillon Initiative). Report of 15 incidentally detected thyroid cancers].
In the framework of the Thyroid initiative Papillon 2001 - 2002 thyroid nodules and sonographically detectable focal lesions with a diameter more than 5 mm were verified in 23.1% of 64.123 persons without a history of thyroid disease. The frequency of such findings was with 33.0% in 46-65 years old persons three times higher then in persons aged 18-30 years (9.6%). In the diagnostic workup thyroid cancer was detected in 15 patients operated on up to now (6 women and 9 men; papillary cancers in 12 cases, follicular cancers in 3 cases) The smallest tumor had a diameter of 1.3 cm, the mean diameter was 2.3 +/- 91 cm. In 3 patients the tumor had invaded the tissue beyond the thyroid capsule, in 4 cases multicentric growth was detected. Lymph node metastases were found in 7/15 cases and distant metastases in 2/15 cases. These result reveal, that thyroid cancer detected by chance may be relatively aggressive. In daily routine, sonographically detectable lesions with poor echogenicity, irregular margins or internal calcifications with a diameter of more than 1 cm should be clarified by fine needle aspiration biopsy.


Safety and effectiveness of cervical vertebroplasty: report of a large cohort and systematic review.
To evaluate retrospectively safety and effectiveness of cervical vertebroplasty (cVP) based on a single-center large cohort. All cVP performed at a single center from January 2001 to October 2014 were included and reviewed. Procedure-related complications (minor and major) were systematically recorded. Effectiveness in terms of analgesia was evaluated using a semi-quantitative grading scale at 1-month follow-up. Risk factors for the occurrence of a procedure-related complication or cement leakage, as well as factors influencing pain relief at 1-month follow-up, were evaluated using a multivariate analysis. One hundred and forty cVP procedures (176 vertebrae) were performed in 130 consecutive patients (88 female, 42 male; mean age = 56 years) during the inclusion period. Among the treated lesions, 80% were bone metastases (mostly from breast cancer), 8% were related to hematological malignancies, and 12% were non-malignant lesions. One fatal complication (0.7%) was related to cement migration in the vertebrobasilar system. Three cervical hematomas were recorded, one of them requiring prolonged oral intubation. The overall rate of major complications was 1.5%. At 1 month, pain reduction was observed in 76% of the cases. Additional surgical fixation was required in 6.1% of the cases. cVP of more than one vertebra during the same session was an independent risk factor for procedure-related complications. Cervical vertebroplasty is a safe technique with an acceptable major complication rate. Its effectiveness in terms of pain relief is good at mid-term follow-up. • Cervical vertebroplasty (cVP) is a safe procedure with a low rate of major complications (1.5%). • cVP provides pain relief in 76% of the cases. • Additional fixation surgery is rarely required after cVP (6.1% of the cases).


Studies on the interaction between steffimycins and DNA.
The complexes formed between steffimycins and DNA were studied using various physicochemical techniques. The binding process has been followed spectrophotometrically or fluorimetrically. The binding parameters n and K, evaluated according to McGhee and Von Hippel, show a good affinity of these antibiotics for the macromolecule. Flow dichroism measurements showed that in the complex with DNA, the antracycline moiety of the steffimycins is intercalated between two base pairs of the macromolecule. The binding experiments with various polydeoxyribonucleotides and with various DNA samples, having different base pair compositions, suggest that an alternate sequence of A-T, such as that of poly[d(A-T)] . poly[d(A-T)], represents a good receptor site for the binding of steffimycins to DNA. The lack of in vivo activity of these antibiotics is discussed.


International variability in diet and requirements of manganese: Causes and consequences.
Manganese (Mn) is an essential trace element that is critical for human health and development. At the turn of the century when diets were based on whole grains, cereals and other traditional foods, Mn intakes (8-9mg/d) were much greater than that prevalent today (2mg/d). As societies have developed, diets have shifted as part of a nutrition transition, to those that are high in processed foods, fat, and sugar. These foods are virtually devoid of Mn. Thus, dietary Mn has declined substantially throughout the world, as confirmed by several wide-scale, total diet studies. International variability in dietary Mn is considerable, due to tremendous diversity in food and culture. In countries where fruit and vegetable intake may be limited, i.e. the United Kingdom, populations may ingest much lower levels of Mn (1.4mg/d) as compared to Asian cultures (4mg/d) which have an abundance of plant foods in their food supply and cuisine. The bioavailability of Mn must be considered, including chemical form, oxidation state, mineral-mineral interactions, presence of dietary components and traditional food processing techniques (milling, germination, malting, fermentation). Manganese toxicity is a public health problem that results from exposure to a naturally high water source or contaminated environment of the soil and/or drinking water. In contrast, inadequate intake is associated with adverse health effects such as diabetes, metabolic syndrome, poor birth outcomes and possibly, cancer. Future studies are recommended to set dietary standards for this mineral in countries that lack recommendations to help achieve optimal health.


Bilateral frontal plane mechanics after unilateral total knee arthroplasty.
To compare frontal plane knee mechanics among the operated and nonoperated limbs after total knee arthroplasty (TKA) and a healthy control limb. A cross-sectional analysis with age-matched control group. A biomechanics and sports medicine laboratory. Subjects (n=16; 8 men, 8 women; mean age, 61+/-7 y; height, 1.71+/-0.10 m; weight, 87.5+/-15.1 kg) and age-matched healthy controls (n=16; 8 men, 8 women; mean age, 63+/-7 y; height, 1.7+/-.09 m; weight 72.5+/-13.9 kg). Not applicable. Peak knee adduction angle, first peak knee adduction moment, and the frontal plane knee angle and moment at loading peak during the stance phase of walking. Peak knee adduction angle (P=.176), and the frontal plane knee angle (P=.116) and moment (P=.260) at loading peak were similar across the operated, nonoperated, and healthy control limbs. The first peak knee adduction moment was higher in the nonoperated limb when compared with the operated limb and with the healthy control (P=.003). First peak knee adduction moment was similar in the operated knee and the healthy control. The greater first peak knee adduction moment in the nonoperated knee indicates a possible mechanism for the predictable deterioration of this knee after unilateral TKA of the contralateral knee.


Investigation into fresh air delivery performance with vortex ring.
An air supply mode based on vortex ring structures was proposed to deliver fresh air for good indoor air quality. This study focused on the influence of air supply parameters, including formation time (T*), supply air velocity (U0), and supply air temperature difference (ΔT), on the fresh air delivery performance of an air vortex ring using numerical simulations. The cross-sectional average mass fraction of fresh air (Ca) was proposed to evaluate the fresh air delivery performance of the air vortex ring supply. The results showed that the convective entrainment of the vortex ring resulted from the combined effect of the induced velocity generated by the rotational motion of the vortex core and the negative pressure zone. When the formation time T* < 3.5, Ca increases with an increase in the formation time but decreases with an increase in the formation time for T* > 3.5. The variation in Ca is insignificant for U0 < 3 m/s or U0 > 3 m/s but decreases with an increase in the supply air temperature difference (ΔT). Thus, the optimal air supply parameters for air vortex ring supply are identified as T* = 3.5, U0 = 3 m/s, ΔT = 0 °C. Compared with the traditional circular and square free air jets, within 25Ds (Ds: the diameter of air supply inlet) downstream from the air inlet, the fresh air delivery performance of the air vortex ring supply is increased by a maximum of nearly 200 %, with an average improvement of approximately 120 %.


A Randomized Controlled Trial Comparing Trainee-Directed Virtual Reality Simulation Training and Box Trainer on the Acquisition of Laparoscopic Suturing Skills.
To compare the proficiency of novices in acquiring laparoscopic suturing skills following training in a virtual reality simulator or box trainer compared to no training. This was a RCT in a university-affiliated teaching hospital recruiting participants who had no laparoscopic suturing experience to have suturing skill training in the virtual reality simulator, box trainer, or no training as control. Trainees were allowed to terminate training when they perceived competence in the procedure. Suturing skills were tested in the box trainer and scored using a modified Global Operative Assessment of Laparoscopic Skills questionnaire by their own self-evaluation and two experienced gynaecological laparoscopists. Of the 36 participants recruited, 27 (75%) had no laparoscopic experience. Participants with no laparoscopic experience took longer to complete training than those with experience (median 90 minutes [interquartile range (IQR) 80-115] vs. 55 min [IQR 40-65], respectively; P = 0.044). There were no differences in successful completion of the task (7/12 [58.3%], 10/12 [83.3%], 7/12 [58.3%]; P = 0.325), median suturing time in seconds (628 [IQR 460-835], 611 [IQR 434-691], 609 [IQR 540-837]; P = 0.702), mean subjective (mean ± SD 9.8 ± 1.8, 10.4 ± 2.8, 9.3 ± 2.4; P = 0.710), and objective (7.2 ± 1.8, 8.2 ± 2.1, 7.6 ± 1.7; P = 0.426) modified Global Operative Assessment of Laparoscopic Skills score in the simulator, pelvic trainer, and control groups, respectively. The intraclass correlation coefficient of the two reviewers was 0.422 (95% CI 0.159-0.717). Trainees were unable to accurately assess themselves as to skill level in laparoscopic suturing. A longer training time is required for novices to master laparoscopic suturing using a simulator or box trainer.


Medical emergency team calls in the radiology department: patient characteristics and outcomes.
We sought to identify the characteristics of patients who experience medical emergency team calls in the radiology department (MET-RD) and the relationship between these characteristics and patient outcomes. Retrospective review of 111 inpatient MET-RD calls (May 2008-April 2010). Academic medical centre with a well established MET system. The characteristics of patients before, during and after transport to radiology were extracted from medical records and administrative databases. These characteristics were compared between patients with good and poor outcomes. The majority of patients who experience MET-RD calls had a Charlson Comorbidity Index ≥4 and were from non-intensive care units (60%). Almost half (43%) of MET-RD calls occurred during patients' first day in hospital. Patients commonly arrived with nasal cannula oxygen (38%), recent tachypnoea (28%) and tachycardia (34%). A minority (16%) fulfilled MET call criteria in the 12 h before the MET-RD. MET-RD etiologies were cardiac (41%), respiratory (29%) or neurological (25%), and occurred most frequently during CT (44%) and MRI (22%) testing. Post MET-RD, the majority of patients (70%) required a higher level of care. Death before discharge (25%) was associated with need for cardiovascular support prior to RD transport (p=0.02), need for RD monitoring (p=0.02) and need for heightened RD surveillance (p=0.04). The majority of patients who experienced MET-RD calls came from non-intensive care units, with comorbidities and vital sign alterations prior to arrival at the RD. Risk appeared to be increased for those requiring CT and MRI. These findings suggest that prior identification of a subset of patients at risk of instability in the RD may be possible.


Ultrasound findings of subacute thyroiditis: a single institution retrospective review.
High resolution ultrasonography features have also been described as having a useful supporting role in the diagnosis of subacute granulomatous thyroiditis (ST), and images are generally characterized by heterogeneous hypoechoic areas of the affected tissue with lack of flow on color Doppler US. To determine the sonographic features of subacute granulomatous thyroiditis. We reviewed the medical records of patients referred at the Endocrine and Metabolic Unit of our Institution between January 2010 and December 2011. A total of 7520 patients were evaluated in our department between January 2010 and December 2011. Among them, 22 (0.3%) patients had a diagnosis of ST (19 women and 3 men, 45.4 ± 9.7 year; range, 33-62 years). Ultrasound examination showed bilateral ST in 64% of patients. Thyroid volume was 13.2 ± 7.7 mL, without difference if ST was unilateral (13.2 ± 7.1 mL) or bilateral (13.9 ± 8.3 mL). On grayscale US, heterogeneous diffusely or focally marked hypoechoic areas, like "lava flow", were found in all the lesions. Our data confirm the high sensitivity of US in the diagnosis of ST: diffuse hypoechoic and confluent areas with the characteristic features like "lava flow".


High-resolution genetic profile of viral genomes: why it matters.
The approval of novel antiviral treatments for hepatitis C virus (HCV) infection provides a great example of research driven medicine in action. However, the emergence of resistant viral strains to existing treatments reminds us of the ongoing challenge that we still face in HCV therapy. What can be done to minimize the health risk posed by viral variants that develop resistance and cause failure of therapy? Here we propose that a high-resolution genetic profiling approach that can assess the function at a single nucleotide/amino acid resolution, may provide a solution. We further discuss the potential application of this methodology in resolving viral resistance through the following three aspects: (1) high-resolution mapping of inflexible regions on the viral genome to identify better drug targets; (2) exhaustive drug resistance profiles to facilitate next-generation drug design; (3) coupled with closely monitoring within-host virus quasi-species, drug resistance profiles can aid in optimized drug combination and personalized medicine in HCV treatments.


Julia Gordon Arrowood (1900 - 1984): A Brilliant Anesthesiologist and a Woman of Many Firsts in Medicine.
After a brief "golden age" in the late 1800s, the patriarchal establishment fought back and women faced increasing restrictions in practicing medicine. In 1900, 18.2% of all physicians in the city of Boston were women, but this number decreased to 8.7% by 1930. The relatively young field of anesthesiology was one of the more welcoming specialties for women during this time. History has been unkind to these early female trailblazers who have often been overlooked in favor of the men in their fields. Julia Gordon Arrowood (1900-1984) was a forerunner for women in medicine and a prominent anesthesiologist in Boston from the 1930s until the 1950s. Her work included not only clinical medicine, but also research and teaching. She attended Boston University School of Medicine, graduating as valedictorian in the class of 1933. She interned at Belmont Hospital in Worcester, MA where she decided on a career in anesthesiology. She was accepted as a resident at Massachusetts General Hospital (MGH) by chief-anesthetist Henry Beecher in 1935, thereby becoming the first woman anesthesiology resident in Massachusetts. She remained at MGH and was named Acting Chief of Anesthesia in 1943. In 1944, she became president of the New England Society of Anesthesiologists, another first for a woman. In 1946, she joined Reginald Smithwick's team as Chief of Anesthesia at Massachusetts Memorial Hospital, Boston, and concurrently held the position of Professor of Anesthesiology at Boston University School of Medicine. Arrowood led many of the earliest studies on spinal anesthesia, muscle relaxants, and spinal headaches. In 1957, she moved to Kentucky and joined the United Mine Workers hospital system where she worked until her retirement in 1970. Women such as Julia Arrowood remain underrepresented in the annals of the history of medicine. Much work is needed to recognize the many contributions made by women physicians and to provide equal opportunities, pay, and status.


In vivo modulation of rat hypothalamic histamine release by the histamine H3 receptor ligands, immepip and clobenpropit. Effects of intrahypothalamic and peripheral application.
We investigated the effect of the new potent and selective histamine H3 receptor agonist, immepip, and the histamine H3 receptor antagonist, clobenpropit, on in vivo neuronal histamine release from the anterior hypothalamic area of urethane-anesthetized rats, using microdialysis. Intrahypothalamic perfusion with immepip at concentrations of 1 and 10 nM reduced histamine release to 75% and 35% of its basal level, respectively. Peripheral injection of immepip (5 mg/kg) caused a sustained decrease in histamine release of 50%. Clobenpropit potently increased histamine release after intrahypothalamic perfusion. The maximal increase in histamine release was 2-fold, observed at a concentration of 10 nM clobenpropit. Peripheral injection of clobenpropit (5-15 mg/kg) increased histamine release to about 150% of the basal value. A more marked increase in histamine release was found after injection of the histamine H3 receptor antagonist, thioperamide (5 mg/kg). In conclusion, intrahypothalamic perfusion of the histamine H3 receptor agonist, immepip and the histamine H3 receptor antagonist, clobenpropit, potently and oppositely modulated in vivo histamine release from the anterior hypothalamic area. The decreased histamine release after peripheral injection of immepip indicates that this novel agonist readily crosses the blood-brain barrier, making it a potential candidate for in vivo histamine H3 receptor studies. The differential increase in histamine release after peripheral injection of clobenpropit and thioperamide is discussed.


Association of IgG4-Related Disease With History of Malignancy.
IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unclear etiology. Some studies suggest that IgG4-RD predisposes patients to malignancy or is a forme fruste of cancer, but we have frequently observed IgG4-RD patients who have a history of malignancy preceding the clinical onset of IgG4-RD. This study was undertaken to characterize IgG4-RD in the setting of previous malignancy diagnosis. We identified IgG4-RD patients with a history of invasive malignancy from a well-defined cohort of 125 patients and compared their malignancy history to those of 2 reference groups. First, we calculated a standardized prevalence ratio against general US population estimates from the Surveillance, Epidemiology, and End Results (SEER) database. Second, we identified up to 5 age- and sex-matched controls for each case and calculated the odds of malignancy among those with IgG4-RD compared to controls, using conditional logistic regression. The mean ± SD age at IgG4-RD onset was 50.3 ± 14.9 years, and 61% of the patients were male. Twenty (16%) had been diagnosed as having malignancies (total 21 malignancies) before the diagnosis of IgG4-RD. The observed prevalence of malignancy in this cohort was 2.5 times higher (95% confidence interval [95% CI] 1.1-3.6) than expected compared to the SEER database. Compared to matched controls, the frequency of history of malignancy was >3-fold higher in IgG4-RD patients (95% CI 1.6-6.2). Our findings suggest that, in a subset of patients with IgG4-RD, malignancy may be associated with subsequent IgG4-RD development. Potential explanations include shared risk factors for both IgG4-RD and cancer, the triggering by cancer of autoantigen expression leading to IgG4-RD, and an increased risk of IgG4-RD resulting from cancer treatment.


Epstein Barr virus infection in tree shrews alters the composition of gut microbiota and metabolome profile.
Epstein-Barr virus (EBV) infection is a major global threat; its manifestations range from the absence of symptoms to multiorgan malignancies and various gastrointestinal diseases. Analyzing the composition and metabolomic profile of gut microbiota during acute EBV infection might be instrumental in understanding and controlling EBV. Six tree shrews were inoculated with EBV by intravenous injection. Blood was collected at regular intervals thereafter from the femoral vein to detect EBV and inflammatory biomarker. At the same time, tree shrew faeces were collected for 16 S rRNA gene sequencing and Non-targeted metabolomics analysis. 16 S rRNA gene characterization along with β diversity analysis exhibited remarkable alterations in gut microflora structure with a peak at 7 days post-infection(dpi). Some alterations in the relative richness of bacterial taxon were linked to infectious indicators. Of note, Butyricicoccus relative richness was positively linked to EBV presence in the blood and plasma, the opposite correlation was seen with Variovorax and Paramuribaculum. Non-targeted metabolomics indicated the fecal metabolome profile altered during EBV infection, particularly 7 dpi. The relative abundance of geranic acid and undecylenic acid in stool samples was positively linked to systemic inflammatory biomarkers, and an inverse relationship was reported with the estrone glucuronide, linoleic acid, protoporphyrin IX and tyramine. Collectively, EBV infection in this model correlated with changes in the composition and metabolome profile of the gut microbiota.


Impact of a behavioral weight loss intervention on comorbidities in overweight and obese breast cancer survivors.
Comorbid medical conditions are common among breast cancer survivors, contribute to poorer long-term survival and increased overall mortality, and may be ameliorated by weight loss. This secondary analysis evaluated the impact of a weight loss intervention on comorbid medical conditions immediately following an intervention (12 months) and 1-year postintervention (24 months) using data from the Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial-a phase III trial which was aimed at and successfully promoted weight loss. ENERGY randomized 692 overweight/obese women who had completed treatment for early stage breast cancer to either a 1-year group-based behavioral intervention designed to achieve and maintain weight loss or to a less intensive control intervention. Minimal support was provided postintervention. New medical conditions, medical conditions in which non-cancer medications were prescribed, hospitalizations, and emergency room visits, were compared at baseline, year 1, and year 2. Changes over time were analyzed using chi-squared tests, Kaplan-Meier, and logistic regression analyses. At 12 months, women randomized to the intervention had fewer new medical conditions compared to the control group (19.6 vs. 32.2 %, p < 0.001); however, by 24 months, there was no longer a significant difference. No difference was observed in each of the four conditions for which non-cancer medications were prescribed, hospital visits, or emergency visits at either 12 or 24 months. These results support a short-term benefit of modest weight loss on the likelihood of comorbid conditions; however, recidivism and weight regain likely explain no benefit at 1-year postintervention follow-up.


An empirical and modelling approach to the evaluation of cruise ships' influence on air quality: The case of La Paz, Mexico.
Maritime activity has diverse environmental consequences impacts in port areas, especially for air quality, and the post-COVID-19 cruise tourism market's potential to recover and grow is causing new environmental concerns in expanding port cities. This research proposes an empirical and modelling approach for the evaluation of cruise ships' influence on air quality concerning NO2 and SO2 in the city of La Paz (Mexico) using indirect measurements. EPA emission factors and the AERMOD modelling system coupled to WRF were used to model dispersions, while street-level mobile monitoring data of air quality from two days of 2018 were used and processed using a radial base function interpolator. The local differential Moran's Index was estimated at the intersection level using both datasets and a co-location clustering analysis was performed to address spatial constancy and to identify the pollution levels. The modelled results showed that cruise ships' impact on air quality had maximum values of 13.66 μg/m3 for NO2 and 15.71 μg/m3 for SO2, while background concentrations of 8.80 for NOx and 0.05 for SOx (μg/m3) were found by analysing the LISA index values for intersections not influenced by port pollution. This paper brings insights to the use of hybrid methodologies as an approach to studying the influence of multiple-source pollutants on air quality in contexts totally devoid of environmental data.


Projections to the inferior olive of the cat. II. Comparisons of input from the gracile, cuneate and the spinal trigeminal nuclei.
The present experiments compared the projections to the inferior olive of the cat from the gracile, cuneate and spinal trigeminal nuclei. A differential labeling strategy was used for these comparisons. It was found that all three somatic sensory nuclei project to portions of all three major divisions of the contralateral inferior olive. The spinal trigeminal n. may also project less densely to the ipsilateral medial accessory olive. Projections to the dorsal accessory nucleus (DAO) and the medially-adjacent ventral lamella of the principal nucleus are roughly somatotopically organized. Although there is considerable overlap between the projection zones, the gracile n. projects predominantly to lateral DAO, the cuneate n. projects predominantly to medial DAO, and the spinal trigeminal nucleus pars caudalis projects predominantly to the most medial portions of DAO and the ventral lamella of principal olive. Projections to the medial accessory olive, on the other hand, are not as highly organized. Instead, they overlap extensively within a small egg-shaped area in the middle of the caudal half of the nucleus. Whereas all portions of the gracile and cuneate nuclei project to the inferior olive, only the pars caudalis of the spinal trigeminal nucleus appears to do so. These results were compared with the three available olivocerebellar maps as well as with the available behavioral and electrophysiological evidence on cerebellar somatotopic organization. This comparison indicated that the inputs to the cerebellum from the three second-order somatosensory nuclei via the inferior olive appear to be generally consistent with cerebellar somatotopic organization. This consistency is apparent not only with respect to the longitudinally-organized, vermal and paravermal differences in the anterior lobe, but also with respect to the transversely-organized specific somatotopy of the intermediate zone of the anterior lobe and the paramedian lobule.


Percutaneous irreversible electroporation (IRE) of prostate cancer: Contrast-enhanced ultrasound (CEUS) findings during follow up.
Irreversible electroporation (IRE) is a focal non-thermal ablation technique that can be used to treat prostate cancer (Pca). The objective was to document the evolution of the volume of the prostate gland and the ablation zone after IRE of Pca. A retrospective analysis of the image findings of CEUS 1 day, 6 weeks, 3 months and 6 months after IRE of 25 patients was conducted. The prostate gland volumes and the size of the ablation zones were documented. Changes in volume and size over time were calculated. There was a significant volume reduction of the prostate gland in the first 3 months after ablation. The mean percentage change after 6 weeks was 34.3% with another decrease of 35.0% after 3 months. Volume did not change between month 3 and 6. Size of ablation zone measured in short- and long-axis significantly diminished until 6 months after ablation. CEUS showed a significant involution of the prostate gland during the first 3 months and a significant decrease of the ablation zone during the first 6 months after IRE of prostate cancer.


Impact of initial steroid response on transplant outcomes in children with steroid-resistant nephrotic syndrome.
Limited data suggest children with secondary steroid-resistant nephrotic syndrome (secondary SRNS) have increased risk of recurrence post transplantation. There are no data on the association between secondary steroid resistance and risk of transplant loss. Children who received kidney transplantation between 2000 and 2019 for either primary or secondary SRNS in Australia and New Zealand were included. Children presenting with nephrotic syndrome before 12 months were excluded. Data were gathered from chart reviews and ANZDATA. Transplant survival was estimated using the Kaplan-Meier estimator with Cox modelling used to explore predictors of survival. There were seventy children, 38 (55%) male, median age at presentation 4 years (IQR 2-7) and 46 (66%) Caucasian. Median age at transplant was 11 years (IQR 7-15) and 39 (55%) received living donor transplant. Secondary SRNS occurred in 20/70 (29%). For those with secondary SRNS, 18/20 (90%) had recurrence post-transplant, compared to 18/50 (36%) with primary SRNS (p = 0.001). Every child with history of atopy (n = 11) or with hypoalbuminaemia at time of transplant (n = 13) experienced immediate recurrence. For children with secondary SRNS, 8/18 (44%) with post-transplant recurrence had no response to therapy. For children with primary SRNS, 4/18 (22%) with recurrence had no response to therapy (p = 0.3). Overall, 10-year transplant survival was 47% (95%CI 29-77%) for those with secondary SRNS, compared to 71 (95%CI 57-88%) for those with primary SRNS (p = 0.05). Secondary steroid resistance is strongly associated with SRNS recurrence. Atopy and hypoalbuminaemia at transplant may be novel risk factors for recurrence. Further research is needed to assess if secondary steroid resistance is associated with poorer transplant outcomes. "A higher resolution version of the Graphical abstract is available as Supplementary information".


Quantitative Affinity Interaction of Ubiquitinated and Non-ubiquitinated Proteins with Proteasome Subunit Rpn10.
Recent proteomic profiling of mouse brain preparations using the ubiquitin receptor, Rpn10 proteasome subunit, as an affinity ligand revealed a representative group of proteins bound to this sorbent (Medvedev, A. E., et al. (2017) Biochemistry (Moscow), 82, 330-339). In the present study, we investigated interaction of the Rpn10 subunit of proteasomes with some of these identified proteins: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase, and histones H2A and H2B. The study revealed: (i) quantitative affinity interaction of the proteasome subunit immobilized on a Biacore-3000 optical biosensor cuvette with both the GAPDH (Kd = 2.4·10-6 M) and pyruvate kinase (Kd = 2.8·10-5 M); (ii) quantitative high-affinity interaction of immobilized histones H2A and H2B with the Rpn10 subunit (Kd values of 6.5·10-8 and 3.2·10-9 M, respectively). Mass spectrometric analysis revealed the presence of the ubiquitin signature (GG) only in a highly purified preparation of GAPDH. We suggest that binding (especially high-affinity binding) of non-ubiquitinated proteins to the Rpn10 proteasome subunit can both regulate the functioning of this proteasomal ubiquitin receptor (by competing with ubiquitinated substrates) and promote activation of other pathways for proteolytic degradation of proteins destined to the proteasome.


EGFR inhibitors regulate Ca2+ concentration and apoptosis after PM2.5 exposure based on a lung-mimic microfluidic system.
Air pollution has side effects on human health. Epidemiology studies indicate a positive association between ambient fine particle (PM2.5, or particles less than 2.5 μm in diameter) concentration and lung cancer. However, how fine particles affect lung cancer at the molecular level and related therapeutic methods to address these diseases are unclear. Here, the multi-omics analysis (DNA methylation and transcriptomic) was used to detect human bronchial epithelial cells (HBE), that were exposed to PM2.5 using a quantified, small, portable, and organ-level air-liquid interface microfluidic system that mimics lung functions. The results indicate that 36,838 differentially methylated genes were detected. Of these 33,796 genes were hypomethylated (beta < 0), and 2862 genes were hypermethylated (beta > 0). RNA-Seq analysis demonstrated that 19,489 genes were upregulated (log2FC > 0), and 16,659 were downregulated. Furthermore, the calcium and apoptosis pathways were activated according to multi-omics analysis. The change in EGFR gene expression after PM2.5 exposure was the result of alterations of the cellular DNA methylome in the promoter. Inhibition or down-regulation of EGFR could result in the regulation of the downstream intracellular Ca2+ concentration and apoptosis via the EGFR/PLCγ and EGFR/STAT/Bcl-XL pathways after PM2.5 exposure. EGFR inhibitors decrease the Ca2+ concentration of cells, thereby strengthening the effects of fine particles on apoptosis. In short, the Ca2+ concentration and the apoptosis of cells can be regulated via EGFR related pathway after PM2.5 exposure. The EGFR may be a potentially promising therapeutic target for the treatment of air pollution-induced lung cancer through regulation of the intracellular Ca2+ concentration and apoptosis.


Island pedicle flaps for medial canthus repair.
The medial canthus is a frequent site for skin cancer and reconstruction after Mohs surgery can prove to be challenging. In the literature various reconstruction methods are recommended for these cases. Flap reconstructions are mostly transposition flaps from the glabella, skin with different properties from that in the canthal region, hence mostly requiring correction in a second stage. To ascertain the utility of a different reconstruction method, applying island pedicle flaps for medial canthal lesions and obviating the necessity for second-stage corrections. A review was undertaken of the medical records and photographs of patients who had a pedicle island flap reconstruction for medial canthal defects after Mohs surgery. There were four different possibilities: a pedicle island flap from the cheek, the back of the nose or the glabella or a combination of these flaps. Sixteen patients were reconstructed by pedicle island flaps for defects of the medial canthal area. A follow-up for all patients after 1 year indicated that all patients showed good to excellent results. No cases of web deformation and ectropion were found. This flap is not mentioned in textbooks in reference to the reconstruction of canthal lesions and its value for this particular location is probably underestimated.


Functional exploration of co-expression networks identifies a nexus for modulating protein and citric acid titres in Aspergillus niger submerged culture.
Filamentous fungal cell factories are used to produce numerous proteins, enzymes, and organic acids. Protein secretion and filamentous growth are tightly coupled at the hyphal tip. Additionally, both these processes require ATP and amino acid precursors derived from the citric acid cycle. Despite this interconnection of organic acid production and protein secretion/filamentous growth, few studies in fungi have identified genes which may concomitantly impact all three processes. We applied a novel screen of a global co-expression network in the cell factory Aspergillus niger to identify candidate genes which may concomitantly impact macromorphology, and protein/organic acid fermentation. This identified genes predicted to encode the Golgi localized ArfA GTPase activating protein (GAP, AgeB), and ArfA guanine nucleotide exchange factors (GEFs SecG and GeaB) to be co-expressed with citric acid cycle genes. Consequently, we used CRISPR-based genome editing to place the titratable Tet-on expression system upstream of ageB, secG, and geaB in A. niger. Functional analysis revealed that ageB and geaB are essential whereas secG was dispensable for early filamentous growth. Next, gene expression was titrated during submerged cultivations under conditions for either protein or organic acid production. ArfA regulators played varied and culture-dependent roles on pellet formation. Notably, ageB or geaB expression levels had major impacts on protein secretion, whereas secG was dispensable. In contrast, reduced expression of each predicted ArfA regulator resulted in an absence of citric acid in growth media. Finally, titrated expression of either GEFs resulted in an increase in oxaloacetic acid concentrations in supernatants. Our data suggest that the Golgi may play an underappreciated role in modulating organic acid titres during industrial applications, and that this is SecG, GeaB and AgeB dependent in A. niger. These data may lead to novel avenues for strain optimization in filamentous fungi for improved protein and organic acid titres.


Is blood ammonia influenced by kidney function? A prospective study.
We have investigated whether blood ammonia is increased with worsening CKD. Fifty eight subjects with a range of CKD were recruited for analysis of plasma ammonia and other electrolytes. The concentrations of plasma ammonia were all within the normal reference range and there was no correlation between ammonia and CKD without any effect of dialysis. Blood ammonia is not elevated in or related to the severity of chronic kidney disease.


Evaluation of prefractionation methods as a preparatory step for multidimensional based chromatography of serum proteins.
Prefractionations of proteins prior to their proteolysis, chromatography, and MS/MS analyses help reduce complexity and increase the yield of protein identifications. A number of methods were evaluated here for prefractionating serum samples distributed to the participating laboratories as part of the human Plasma Proteome Project. These methods include strong cation exchange (SCX) chromatography, slicing of SDS-PAGE gel bands, and liquid-phase IEF of the proteins. The fractionated proteins were trypsinized and the resulting peptides were resolved and analyzed by multidimensional protein identification technology coupled to IT MS/MS. The MS/MS spectra were clustered, combined, and searched against the IPI protein databank using Pep-Miner. The identification results were evaluated for the efficacy of the different prefractionation methodologies to identify larger numbers of proteins at higher confidence and to achieve the best coverage of the proteins with the identified peptides. Prefractionation based on SCX resulted in the largest number of identified proteins, followed by gel slices and then the liquid-phase IEF. An important observation was that each of the methods revealed a set of unique proteins, some identified with high confidence. Therefore, for comprehensive identification of the serum proteins, several different prefractionation approaches should be used in parallel.


Poor antenatal care and pregnancy outcome.
To characterize women receiving poor antenatal care and assess their perinatal risk. Computerized data. Public hospital setting Paris (1987-1990). Comparison with representative sample in Ile-de-France region (n = 6423). Poor attenders with less than 3 visits (n = 210) were compared with good attenders with 3 visits or more (n = 5631). Poor attenders were younger and had higher rates of perinatal mortality (4.7%), preterm delivery (Odds ratio 5.2:4.3-6.3) and low birth weight (Odds ratio 4.6:3.7-5.6). Women with poor antenatal care have a greater risk for adverse pregnancy outcome. This risk cannot be attributed to unfavourable living conditions only.


"Magnetic Ni-Zn ferrite anchored on g-C3N4 as nano-photocatalyst for efficient photo-degradation of doxycycline from water".
In the present work, mixed-spinel ferrite anchored onto graphitic carbon nitride (GCN) was synthesized for mineralization of antibiotic pollutant from waste water. A Z-scheme g-C3N4/Ni0.5Zn0.5Fe2O4 nano heterojunction was fabricated by three step procedure: pyrolysis, solution combustion and mechanical grinding followed by annealing. The prepared photocatlyst was tested for degradation of Doxycycline (DC) drug under the natural sun light. Results revealed that the prepared heterojunction has maximum degradation efficiency of 97.10% pollutant in 60 min experiment. The Z-scheme heterojunction between g-C3N4 and Ni-Zn ferrite improves the photoinduced charges separation and protection of redox capability and therby increases the photo degradation efficiency. The scavenging experiments suggested that O2-● and h+ as main active species responsible for degradation of the antibiotic. In addition, the dopant variation can drive the shists in band gap and energy band positiong too which makes then excellent candidates for synthesizing tunable heterostructures with organic semiconductors. The work focusses on designing and developing of saimpler but efficient magnetic heterojunctions with superior redox capability for solar powered waste water treatment.


Process optimization of a moving bed bioreactor undergoing simultaneous nitrification and denitrification for wastewater in the absence of organic carbon.
Moving bed bioreactors are efficient for the removal of nitrogen effluents by simultaneous nitrification and denitrification (SND), which is particularly challenging for effluents with low C/N ratio due to insufficient carbon available for denitrification. The addition of external organic carbon in such cases increases treatment costs. Endogenous degradation of biomass offers a cost-effective and persistent source of carbon. Internal carbon leads to low denitrification rates and optimizing the biomass content leads to a sustainable solution for treating such effluents. The present study aims to optimize the process of SND using endogenous carbon by investigating the effect of operational parameters like dissolved oxygen, influent ammonium (NH4-N) loading, hydraulic retention time (HRT) and carrier filling ratio (CFR). The synthetic wastewater used in the study does not inherently contain any organic carbon, thus indicating the responsible carbon for denitrification to be of internal origin. Using a novel carrier for multispecies biofilm development, initial NH4-N concentration variation showed an insignificant effect on SND efficiency. At higher loading, nitrite accumulation due to incomplete denitrification was observed. The effect of CFR was investigated in a range of 20-35%, beyond which non-homogeneous mixing was caused in the reactor. Under controlled DO and temperature of about 5 mg/L and 28 ± 2°C, respectively, an optimum filling ratio of 35% was finalised, resulting in an SND efficiency of 97.9% at 22 h HRT for high influent NH4-N concentration of 500 mg/L. Bacteriological species identification revealed the coexistence of nitrogen-fixing, aerobic nitrifying and anaerobic denitrifying bacteria in the biofilm growing on the biocarrier.Mechanism of SND occurring in aerobic moving bed bioreactors: Laboratory-scale aerobic Moving Bed Bioreactor setup for a continuous study evaluating the influence of operational parameters on SNDOccurrence of aerobic and anoxic zones in biofilm grown on the surface of novel carriers due to diffusional gradient of dissolved oxygen.


Potential and prognostic factor for belimumab-free remission in patients with systemic lupus erythematosus: a single-center retrospective analysis.
Belimumab is an effective and safe treatment option for systemic lupus erythematosus (SLE). However, data on treatment cessation are lacking. Thus, we investigated belimumab-free remission in SLE patients. SLE patients receiving belimumab in our institute (May 1, 2013-May 31, 2019) were retrospectively identified using electronic health records. Eligibility criteria included receiving belimumab for > 180 days and discontinuation for any reason. BILAG category A or B in at least one organ system indicated a disease flare. Follow-up monitoring during post-treatment at week 52 identified relapse-free and relapse patients. Thirty-one patients received belimumab, and 8 patients were included. Of the 8 patients, 4 relapsed within 52 weeks. At belimumab discontinuation, relapse-free patients achieved lower SELENA-SLEDAI (1 [IQR, 0-2] vs. 7 [IQR, 5.5-8] (p = 0.03)), received significantly less steroid (prednisolone equivalent, 3.0 mg/day [IQR, 2.8-3.2] vs. 9.5 mg/day [IQR, 7.3-13.3], p = 0.02) than relapse patients, and significantly more relapse-free patients achieved SELENA-SLEDAI less than 4 and received prednisolone less than 5 mg/day than relapse patients. Furthermore, on discontinuation day, relapse-free patients tended to have higher C3 (91.0 mg/dL [IQR, 78.8-102.3] vs. 56.0 mg/dL [IQR, 39.8-73.0], p = 0.15) and C4 levels (22.0 mg/dL [IQR, 19.00-26.00] vs. 11.0 mg/dL [IQR, 6.00-16.00], p = 0.08) and less anti-dsDNA antibody (5.2 IU/mL [IQR, 3.8-7.8] vs. 48.0 IU/mL [IQR, 11.5-137.3], p = 0.08) than relapse patients. Belimumab discontinuation can be considered for patients who achieved good responses. Normalization of complement, anti-dsDNA antibody, SELENA-SLEDAI less than 4, and steroid dosage less than 5 mg/day might be prognostic markers for belimumab-free remission.


Marine debris and human impacts on sea turtles in southern Brazil.
Dead stranded sea turtles were recovered and examined to determine the impact of anthropogenic debris and fishery activities on sea turtles on the coast of Rio Grande do Sul State, Brazil. Esophagus/stomach contents of 38 juvenile green Chelonia mydas, 10 adults and sub-adults loggerhead Caretta caretta, and two leatherback Dermochelys coriacea turtles (adult or sub-adult) included plastic bags as the main debris ingested, predominated by white and colorless pieces. The ingestion of anthropogenic debris accounted for the death of 13.2% of the green turtles examined. Signs of damage over the body and carapace indicated that fishing activities caused the death of 13.6% (3/22) of loggerheads and 1.5% (1/56) of green turtles. Therefore, it appears that direct and indirect effects of fishing activities may pose a threat to these species in Brazilian waters. Other sources of plastic debris should be investigated as well as the direct impact of fisheries, especially bottom trawl and gill nets, in order to establish effective conservation action.


A new cross-talk between the aryl hydrocarbon receptor and RelB, a member of the NF-kappaB family.
The discovery of the new crosstalk between the aryl hydrocarbon receptor (AhR) and the NF-kappaB subunit RelB may extend our understanding of the biological functions of the AhR and at the same time raises a number of questions, which will be addressed in this review. The characteristics of this interaction differ from that of AhR with RelA in that the latter appears to be mostly negative unlike the collaborative interactions of AhR/RelB. The AhR/RelB dimer is capable of binding to DNA response elements including the dioxin response element (DRE) as well as NF-kappaB binding sites supporting the activation of target genes of the AhR as well as NF-kappaB pathway. Further studies show that AhR/RelB complexes can be found not only in lymphoid cells but also in a human hepatoma cell line (HepG2) or breast cancer cell line (MDA-MB-231). RelB has been implicated in carcinogenesis of breast cancer for instance and RelB is known to be a critical factor for the function and differentiation of dendritic cells; interestingly the participation of AhR in both processes has been suggested recently, which offers the great potential to expand the scope of the physiological roles of the AhR. There is evidence indicating that RelB may serve as a pro-survival factor, including its ability to promote "inflammation resolution" besides the association of RelB with inflammatory disorders. Based on such information, a hypothesis has been proposed in this review that AhR together with RelB functions as a coordinator of inflammatory responses.


Response of human mesenchymal stem cells to patterned and randomly oriented poly(vinyl alcohol) nano-fibrous scaffolds surface-modified with Arg-Gly-Asp (RGD) ligand.
The aim of this study was to obtain a better insight of how nano-fibrous scaffolds can affect human mesenchymal stem cells responses. Therefore, in this study, using electrospinning technique, poly(vinyl alcohol) (PVA) nano-fibers with two different patterns were prepared. In the first structure, PVA nano-fibers were oriented randomly and in the second structure, nano-fibers were electrospun in such a way that a special pattern was obtained. In order to enhance their stability, scaffolds were cross-linked using glutaraldehyde vapor. RGD immobilization was used to improve cell adhesion properties of the scaffolds. SEM micrographs demonstrated that the cell adhesion was effectively enhanced after RGD immobilization and higher cell densities were observed on RGD-modified scaffolds. Randomly oriented nano-fibers showed better cell adhesion compared to patterned structure. Patterned structure also revealed slightly lower cell viability compared to random nano-fibers. Finally, it was assumed that randomly oriented nano-fibers provide a more favorable surface for cells.


Androgen receptors in colorectal adenomas.
To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17-2.7 X 10(-9) M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P = 0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24-3.1 X 10(-9) M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.


"Protease I" of Escherichia coli functions as a thioesterase in vivo.
Escherichia coli protease I is assayed as an esterase active with certain synthetic model chymotrypsin substrates. However, the gene encoding protease I has the same DNA sequence and genomic location as tesA, a gene that encodes E. coli thioesterase I. We report that both hydrolase activities utilize the same active site and demonstrate that the protein functions as a thioesterase in vivo.


Serum levels of soluble ICAM-1 and VCAM-1 predict pre-clinical cancer.
To investigate whether serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were related to first stage cancer before diagnosis of cancer, we compared serum levels of these adhesion molecules between pre-clinical cases and controls using a nested case-control study method. Cancer cases were recruited from a cohort database of 1465 participants who completed a baseline questionnaire and provided blood samples, and were followed up from 1989 to 2003. They consisted of 15 individuals who died of cancer and 31 individuals newly diagnosed with cancer during the follow-up period. Controls were subjects who did not suffer from cancer, cerebral apoplexy, diabetes mellitus, liver disease, or myocardial infarction during the follow-up period. Using commercially available enzyme-linked immunosorbent assay (ELISA) kits, we showed that serum levels of sVCAM-1, but not sICAM-1 were elevated in cases with pre-clinical or early cancer. We suggest that elevated serum levels of sVCAM-1 might serve as a possible marker for detecting pre-clinical or early cancer.


Motor correlates of phototaxis and associative learning in Hermissenda crassicornis.
Motor correlates of Hermissenda phototactic behavior and their modification by associative training were examined. Anatomical studies indicated the posterior three-fourths of the foot to be innervated by nerve P1 while the anterior portion was innervated by nerve P2. Bilateral lesions of either P1 or P2 pedal nerves in untrained animals reduced phototactic behavior. Extracellular recordings of pedal nerves from untrained animals revealed significant increases in total multi-unit activity (MUA) during a light presentation. Prominent components of nerve P2 activity were synchronous bursts apparent in peri-stimulus time (PST) histograms. Burst frequency was increased by light. Associative training resulted in significant decreases in light-evoked MUA frequency in P1 and light-evoked burst frequency in P2. Intracellular recordings were obtained from three classes of putative motoneurons with axons in P2. These were located using cobalt backfills and verified for each preparation by simultaneous extracellular recording from P2. The characteristic pattern of activity of these cells in the dark and its modulation by light was established.


Temporal and spatial MRI responses to subsecond visual activation.
The temporal and spatial characteristics of oxygenation-sensitive MRI responses to very brief visual stimuli (five Hz reversing black and white checkerboard pattern versus darkness) were investigated (nine subjects) by means of serial single-shot gradient-echo echo-planar imaging (2.0 T, TR=400 ms, mean TE=54 ms, flip angle 30 degrees). The use of a 0.2-s stimulus and a 90-s control phase resulted in an initial latency phase (about 2 s, no signal change), a positive MRI response (2.5% signal increase peaking at 5 s after stimulus onset), and a post-stimulus undershoot (1% signal decrease peaking at 15 s after stimulus onset) lasting for about 50-60 s. The finding that a subsecond visual stimulus elicits both a strong positive MRI response and a long-lasting undershoot provides further evidence for the neuronal origin of slow signal fluctuations seen in the absence of functional challenge and their utility for mapping functional connectivity. The additional observation that a reduction of the inter-stimulus control phase from 90 s to 9.8 s does not seem to affect the spatial extent of cortical activation in pertinent maps is of major relevance for the design and analysis of "event-related" MRI studies.


Efficacy of echo-Doppler examination for the evaluation of renovascular disease.
The accuracy of the diagnosis of renal artery stenosis using noninvasive echo-Doppler velocimetry was compared with that of angiography in 40 renal arteries. The duplex-Doppler signals were detected through the muscle of the back (the translumbar approach). Renal artery stenosis was diagnosed by three objectively defined Doppler parameters, the acceleration index (AI), the acceleration time (AT), and the acceleration time ratio (ATR). The normal range obtained on 11 control subjects was defined as AI greater than or equal to 3.78, AT less than or equal to 0.07 s, and ATR less than or equal to 1.35. High technological success (98%) was obtained using the translumbar approach. In comparison with angiography (cases of significant stenosis), the accuracy of the echo-Doppler method using the criteria of the AI was 95%, the sensitivity was 100%, and the specificity was 93%. This noninvasive method may be one of the most accurate screening methods for diagnosing significant renal artery stenosis.


Construction of transgenic Bacillus mucilaginosus strain with improved phytase secretion.
To construct a transgenic Bacillus mucilaginosus strain to increase the secretion capability of a wild-type isolate of B. mucilaginosus D4B1 to hydrolyse phytate phosphorus, which can be used as a microbial fertilizer in field application. We constructed a phytase secreting expression vector pSP43 with a mini-Tn5 transposon and a Aspergillus fumigatus phytase expression cassette. The vector pSP43 was successfully transferred into the wild-type B. mucilaginosus using the particle bombardment method, and three transgenic strains with a stable copy of phytase expression cassette integrated into the chromosome of the B. mucilaginosus by Tn5 transposition were selected. The phytase activity of the engineered strains increased 36-46-fold when compared with the wild-type strain of D4B1. The A. fumigatus phytase gene can be expressed under the direction of p43 promoter in B. mucilaginosus. The expression protein is secreted extracellularly and newly constructed strains showed a high phytase activity. A transgenic Bacillus strain by the particle bombardment method was constructed.


Ocrelizumab-treated patients with relapsing multiple sclerosis show volume loss rates similar to healthy aging.
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by two major and interconnected hallmarks: inflammation and progressive neurodegeneration. The aim of this work was to compare neurodegenerative processes, in the form of global and regional brain volume loss rates, in healthy controls (HCs) and in patients with relapsing MS (RMS) treated with ocrelizumab, which suppresses acute inflammation. Whole brain, white matter, cortical gray matter, thalamic, and cerebellar volume loss rates were assessed in 44 HCs that were part of a substudy in the OPERA II randomized controlled trial (NCT01412333) and 59 patients with RMS enrolled in the same substudy as well as age- and sex-matched patients in OPERA I (NCT01247324) and II. Volume loss rates were computed using random coefficients models over a period of 2 years. Ocrelizumab-treated patients showed global and regional brain volume loss rates that were approaching that of HCs. These findings are consistent with an important role of inflammation on overall tissue loss and the role of ocrelizumab in reducing this phenomenon.


A novel model based on disulfidptosis-related genes to predict prognosis and therapy of bladder urothelial carcinoma.
Disulfidptosis is a novel type of cell death induced by disulphide stress that depends on the accumulation of cystine disulphide, causing cytotoxicity and triggering cell death. However, the direct prognostic effect and regulatory mechanism of disulfidptosis-related genes in bladder urothelial carcinoma (BLCA) remain unclear. To explore the role of 10 disulfidptosis-related genes, the multiomic data of 10 genes were comprehensively analysed. Next, based on seven disulfidptosis-related differentially expressed genes, a novel disulfidptosis-related gene score was developed to help predict the prognosis of BLCA. Immunohistochemistry, EDU, Real-time PCR and western blot were used to verify the model. Significant functional differences were found between the high- and low-risk score groups, and samples with a higher risk score were more malignant. Furthermore, the tumour exclusion and Tumour Immune Dysfunction and Exclusion scores of the high-risk score group were higher than those of the low-risk score group. The risk score was positively correlated with the expression of immune checkpoints. Drug sensitivity analyses revealed that the low-risk score group had a higher sensitivity to cisplatin, doxorubicin, docetaxel and gemcitabine than the high-risk score group. Moreover, the expression of the TM4SF1 was positively correlated with the malignancy degree of BLCA, and the proliferation ability of BLCA cells was reduced after knockdown TM4SF1. The present study results suggest that disulfidptosis-related genes influence the prognosis of BLCA through their involvement in immune cell infiltration. Thus, these findings indicate the role of disulfidptosis in BLCA and its potential regulatory mechanisms.


The morphological and biochemical response of avian embryonic sympathoadrenal cells to nerve growth factor is developmentally regulated.
Cellular differentiation is a stepwise process where environmental factors are essential key components to direct cells to their final phenotype. The sympathoadrenal (SA) system is one of the principal models used to study the role of environmental factors in the development of the peripheral nervous system. Two major cell types originate from the SA progenitor: the principal neurons of the sympathetic ganglia and the chromaffin cells of the adrenal medulla. These cells are directed to their final phenotype by a series of environmental factors, of which nerve growth factor (NGF) and glucocorticoids, are the best studied. Previously, we have shown that 11-day embryonic chick sympathetic cell cultures increased their neuropeptide Y (NPY) protein and mRNA levels in the presence of NGF. In contrast, NGF had no such effect in chromaffin cell cultures from the same developmental stage. These results were unexpected since both cells types respond morphologically to NGF. To determine if these cells can gain or lose their capacity to respond to NGF, morphological and biochemical studies were done at earlier stages using immunocytochemical, radioimmunoassay and polymerase chain reaction (PCR) techniques. Interestingly we found that in E-7 chromaffin cells there is a biochemical and morphological response to NGF, while E-7 sympathetic cells lack this response. Our observations show a developmental point of regulation of morphological and biochemical properties by NGF and reveal an age dependent capacity of SA cells to acquire or lose competence to an environmental factor.


The complete assignment of the 13C NMR spectra of lasalocid and the sodium salt-complex of the antibiotic.
All thirty-four signals observed in the 13C nmr of both the free acid form (Ia) and sodium salt (Ib) of the polyether antibiotic lasalocid have been assigned. This was achieved using model compounds such as 3-methylsalicylic acid, the retroaldol ketones from both lasalocid and lysocellin and a gamma-lactone from a third polyether, salinomycin. The last assignments to be made were accomplished using biosynthetically enriched samples of the antibiotic.


A Meta-analysis of Transcranial Magnetic Stimulation in Obsessive-Compulsive Disorder.
Obsessive-compulsive disorder (OCD) is a debilitating illness with substantial morbidity. Although pharmacological and behavioral evidence-based treatments have shown efficacy, many patients remain unresponsive to this first-line care. Repetitive transcranial magnetic stimulation (rTMS) has shown significant promise for patients with treatment-refractory affective disorders. Therefore, we conducted a meta-analysis of randomized controlled trials to examine the therapeutic benefit of rTMS in patients with OCD and explore moderators of its treatment effects. PubMed (1997-Dec 31, 2022) and PsycINFO were searched for randomized sham-controlled trials of rTMS to treat OCD using the following terms: "obsessive-compulsive disorder," "transcranial magnetic stimulation," and "randomized controlled trial." Clinical characteristics and effect sizes were extracted from 25 randomized controlled trials (860 participants). A random effects model calculated the effect sizes for treatment efficacy and treatment response using the clinician-rated Yale-Brown Obsessive Compulsive Scale. Across randomized controlled trials, rTMS exhibited a moderate therapeutic effect (g = 0.65) on OCD symptom severity and a 3-fold increased likelihood of treatment response (relative risk = 3.15) compared with sham conditions. Greater improvement in comorbid depression severity corresponded with greater treatment effects of rTMS on OCD symptom severity. In addition, longer rTMS sessions and fewer overall sessions predicted greater clinical improvement. rTMS is moderately effective for reducing OCD symptom severity. It holds potential to serve as a therapeutic intervention, particularly for patients with OCD who have failed standard treatments and those with comorbid depression. Further research is needed to optimize rTMS protocols and evaluate the long-term efficacy of rTMS for OCD.


[The Silver-Russell syndrome].
The authors describe a case of Silver-Russell Syndrome with severe deficit growth. They display the major and minor features of the syndrome, and discuss about the possible pathogenetic causes.


Expression and localization of membrane type 1 matrix metalloproteinase in tooth tissues.
Matrix metalloproteinases (MMPs) have been detected in forming dental enamel and are thought to play an important role during enamel biomineralization. Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane bound member of the MMP gene family that has previously been shown to be expressed by cells associated with bone and cartilage formation (osteoclasts, osteoblasts and chondrocytes). Thus, we asked if MT1-MMP was also expressed by the cells responsible for the formation of enamel and dentin. A porcine MT1-MMP cDNA composed of 3284 bp was isolated from an enamel organ-specific cDNA library. Multiple tissue Northern blot analysis revealed that the MT1-MMP message was expressed highly in the enamel organ and pulp organ when compared to the expression levels observed in other non-mineralizing tissues. Northern blot analysis of stage-specific enamel organs (early secretory, late secretory, or maturation stage) and their corresponding pulp organs revealed that MT1-MMP expression increased as the dentin matured. In the enamel organs, however, the MT1-MMP message level became reduced only during the late secretory stage. Immunohistochemical analysis showed that MT1-MMP was present on the surface of the cells (ameloblasts and odontoblasts) responsible for dentin and enamel formation. Thus, MT1-MMP is highly expressed in developing tooth tissues and may play a role in the biomineralization of enamel and dentin.


Salivary cortisol estimation to assess adrenal status in children with fluid unresponsive septic shock.
We evaluated the adrenal status by estimating baseline and ACTH stimulated salivary cortisol in 51 children with fluid unresponsive septic shock at 30 and 60 minutes, and basal salivary cortisol (9-11 am) in 79 healthy children. The baseline salivary cortisol (median,IQR) among patients (19.8, 7.2-42.4 nmol/L) was higher than healthy children (2.6, 1.3-7.6 nmol/L) (P=0.001). Non-survivors and those with catecholamine refractory shock had higher baseline cortisol level, though difference was statistically insignificant. Absolute adrenal insufficiency (baseline salivary cortisol <1.3nmol/L) was diagnosed in 8 (15.7%) patients. Relative adrenal insufficiency (rise in cortisol level above baseline value after stimulation <25nmol/L) was observed in 68.6% of all patients; 71.9% among non-survivors, and in 71.4% patients with catecholamine refractory shock. Salivary cortisol estimation appears to be feasible in children with septic shock. Relative adrenal insufficiency is common in these children.


Working with a statistician.
This chapter presents some guidelines for working with a statistician, beginning with when and why you should consult one. We emphasize the importance of good communication between the statistician and the client and the need for clearly defined tasks and a timetable. Other considerations, such as security, confidentiality, and business arrangements are discussed.


Retrospective audit to determine the diagnostic accuracy of Primovist-enhanced MRI in the detection of hepatocellular carcinoma in cirrhosis with explant histopathology correlation.
This study aims to determine the diagnostic accuracy of Primovist-enhanced MRI in the detection of hepatocellular carcinoma (HCC) in cirrhosis, using liver explant histopathology correlation. Thirty patients underwent a Primovist-enhanced MRI prior to liver transplantation for cirrhosis at the Princess Alexandra Hospital from 2006 to June 2012. Pre-contrast T1, T2 and post-Primovist arterial, portal venous and delayed hepatobiliary phase sequences were routinely obtained. A retrospective audit of MRI reports determined whether HCCs was identified on pre-transplantation imaging. Results were correlated to the explant liver histopathology. Specificity and sensitivity of Primovist in HCC identification in cirrhosis was determined. The time interval between preoperative MRI and transplantation ranged from the day of transplantation to 112 weeks pre-transplantation. Thirty-nine HCCs were identified histologically in explants. Fifteen HCCs were identified on pre-transplant MRI in 11 patients, ranging from 11 to 43 mm, all confirmed on histopathology. Fourteen MRI studies identified no lesion, concordant on histology. Twenty-four either well or moderately differentiated HCCs were identified on histopathology, all of which were less than 17 mm, were not depicted on MRI. No poorly differentiated HCCs were present in the explants. Two regenerative nodules were correctly identified on MRI. This correlated to a sensitivity of 42.5%, specificity of 100% and a positive predictive value of 100% and negative predictive value of 39.5%. Primovist-enhanced MRI is very accurate in the identification of HCC in cirrhosis, especially if the tumour is greater than 17 mm and undifferentiated. However, sensitivity is reduced for well- and moderately differentiated HCC less than 17 mm.


Immunophenotypic dissection of normal hematopoiesis.
Flow cytometry immunophenotyping is essential for diagnosis, classification and monitoring of clonal hematopoietic diseases, particularly of hematological malignancies and primary immunodeficiencies. Optimal use of immunophenotyping for these purposes requires detailed knowledge about the phenotypic patterns of normal hematopoietic cells. In the past few decades, flow cytometry has benefited from technological developments allowing simultaneous analysis of multiple antigen stainings with ≥3-35 distinct fluorochrome-conjugated antibodies for increasingly higher numbers of cells. These advances have contributed to expand our knowledge about the phenotypic differentiation profiles of normal hematopoietic cells, from uncommitted CD34+ precursors in the bone marrow (BM) and peripheral blood (PB), to the several hundreds of populations of circulating myeloid and (B and T) lymphoid cells identified so far. Detailed dissection of the normal phenotypic profiles of hematopoietic cells has settled the basis for identification of aberrant phenotypes on leukemia and lymphoma cells. Thus, it has contributed to: i) more sensitive identification of leukemia/lymphoma cells (especially when represented at low frequencies in a sample), and ii) more accurate classification of hematological malignancies. In this manuscript, we review the major phenotypic features of hematopoietic cells, from the more immature BM CD34+ precursors committed to the myeloid and lymphoid lineages toward mature hematopoietic cells circulating in PB (e.g. neutrophils, monocytes, basophils, eosinophils, dendritic cells, erythroid cells, and B- and T-cells) and those homing to other tissues (e.g. plasma cells, mast cells).


Low pH-induced release of diphtheria toxin A-fragment in Vero cells. Biochemical evidence for transfer to the cytosol.
When Vero cells with surface-bound 125I-labeled, nicked diphtheria toxin were exposed to pH 4.5, two polypeptides of Mr 20,000 and 25,000 became protected against externally applied Pronase E. The 20-kDa polypeptide appears to be the toxin A-fragment, whereas the 25-kDa polypeptide must be derived from the B-fragment. Permeabilization of the cells with saponin allowed efflux of the 20-kDa fragment to occur, whereas most of the 25-kDa polypeptide remained associated with the cells. A number of compounds and conditions which protect cells against diphtheria toxin prevented the protection against Pronase E. Protection of the 25-kDa polypeptide occurred even when the transmembrane proton gradient (delta pH) was dissipated by acidification of the cytosol, whereas protection and release of the A-fragment were prevented under these conditions. Electrical depolarization and ATP depletion of the cells did not inhibit protection and release of the A-fragment. The data indicate that delta pH is required for the transfer of the A-fragment to the cytosol, whereas the insertion of part of the B-fragment into the membrane occurs at low pH, even in the absence of a delta pH.


Traumatic pediatric cataract: a decade of follow-up after Artisan aphakia intraocular lens implantation.
To describe the long-term clinical outcome of Artisan((R)) aphakia intraocular lens (IOL; Ophtec, Groningen, The Netherlands) implantation in five aphakic eyes of five children, without capsular support, after cataract extraction following penetrating ocular trauma. The charts of the five children were retrospectively reviewed. The data collected included follow-up time, nature of injury, age at cataract extraction and IOL implantation, visual outcome, endothelial cell counts, complications, and subsequent surgical interventions. Average follow-up was 11.0 years (range, 8.0-14.6 years). All eyes had a corneal perforation with various degrees of anterior segment injury. Mean patient age at lens extraction was 7.8 years (range, 5.6-10.2 years). Mean age at Artisan aphakia IOL implantation was 7.9 years (range, 5.7-10.2 years). The best spectacle-corrected visual acuity at last follow-up was 20/40 or better in four eyes. Mean endothelial cell loss compared with the healthy fellow eye was 40%. No patients experienced IOL dislocation, corneal decompensation, chronic anterior uveitis, cystoid macular edema, or iris atrophy. One eye had a retinal detachment 19 months after primary injury and needed vitreoretinal surgery. The Artisan aphakia IOL offers a useful alternative for correction of traumatic childhood aphakia. Although we only have results of a small number of patients, taking into account our long follow-up period, we feel that implantation of the Artisan aphakia IOL can be considered a treatment option in aphakic eyes of children that lack capsular support due to trauma.


Detection of acute tubulointerstitial rejection by proteomic analysis of urinary samples in renal transplant recipients.
This study investigates proteomic analysis of urinary samples as a non-invasive method to detect acute rejection of renal allografts. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was used to analyze urinary samples in 19 patients with different grades of subclinical or clinical acute rejection (BANFF Ia to IIb), 10 patients with urinary tract infection and 29 patients without evidence of rejection or infection. A distinct urinary polypeptide pattern identified 16 out of 17 cases of acute tubolointerstitial rejection, but was absent in two cases of vascular rejection. Urinary tract infection resulted in a different polypeptide pattern that allowed to differentiate between infection and acute rejection in all cases. Potentially confounding variables such as acute tubular lesions, tubular atrophy, tubulointerstitial fibrosis, calcineurin inhibitor toxicity, proteinuria, hematuria, allograft function and different immunosuppressive regimens did not interfere with test results. Blinded analysis of samples with and without rejection showed correct diagnosis by CE-MS in the majority of cases. Detection of acute rejection by CE-MS offers a promising non-invasive tool for the surveillance of renal allograft recipients. Further investigation is needed to establish polypeptide patterns in vascular rejection and to explore whether changes in the urinary proteome occur before the onset of histologically discernible rejection.


A Case Study Using Accelerometers to Identify Illness in Ewes following Unintentional Exposure to Mold-Contaminated Feed.
Sensor technologies can identify modified animal activity indicating changes in health status. This study investigated sheep behavior before and after illness caused by mold-contaminated feed using tri-axial accelerometers. Ten ewes were fitted with HerdDogg biometric accelerometers. Five ewes were concurrently fitted with Axivity AX3 accelerometers. The flock was exposed to mold-contaminated feed following an unexpected ration change, and observed symptomatic ewes were treated with a veterinarian-directed protocol. Accelerometer data were evaluated 4 days before exposure (d -4 to -1); the day of ration change (d 0); and 4 days post exposure (d 1 to 4). Herddogg activity index correlated to the variability of minimum and standard deviation of motion intensity monitored by the Axivity accelerometer. Herddogg activity index was lower (p < 0.05) during the mornings (0800 to 1100 h) of days 2 to 4 and the evening of day 1 than days -4 to 0. Symptomatic ewes had lower activity levels in the morning and higher levels at night. After accounting for symptoms, activity levels during days 1 to 4 were lower (p < 0.05) than days -4 to 0 the morning after exposure. Results suggest real-time or near-real time accelerometers have potential to detect illness in ewes.


Analysis of early complications after radical cystectomy: results of a collaborative care pathway.
We examined our recent series of patients who underwent radical cystectomy to determine and analyze the early perioperative morbidity of the procedure in a contemporary series treated with the guidance of a clinical pathway. We reviewed the records of 304 consecutive patients who underwent radical cystectomy from December 1995 to July 2000. We specifically evaluated complications that developed within 30 days of the procedure. Potential variables predictive of early morbidity were analyzed, including patient age, gender, race, American Society of Anesthesiologists score, type of urinary diversion, smoking history, estimated blood loss, transfusion requirement, pathological stage and operative time. The overall minor complication rate was 30.9% (94 of 304 patients). Postoperative ileus was the most common minor complication, affecting 54 patients (18%). Increased blood loss and major complications predicted a significantly higher likelihood of ileus on multivariate analysis (p = 0.02 and 0.001, respectively). Major complications in 15 patients (4.9%) correlated with higher American Society of Anesthesiologists score, surgical intensive care unit admission and transfusion requirement (p = 0.01, <0.001 and 0.001, respectively). The early mortality rate was 0.3% (1 patient). Within the framework of a clinical pathway, radical cystectomy can be performed safely with an acceptable rate of early minor and major complications. Delay in the return of bowel function is the most common minor complication. Increased estimated blood loss, transfusion requirement and a major complication predicted a higher likelihood of postoperative ileus. The acceptable rate of early morbidity in this series in a 5-year period validates its use in patients undergoing radical cystectomy.


Assessment of gestational age by ultrasonic measurement of the femur length.
The effectiveness of ultrasonic femur length measurement from 12 to 40 week's gestation, as a means of assessing fetal age, was tested and compared with that of biparietal cephalometry. The femur length and biparietal diameter (BPD) were obtained from 471 measurements, from pregnant women with confirmed datings, using real-time scanning with a 3,5 mHz transducer frequency. Using a freeze frame and electronic calipers, the mean value of three consecutive measurements of the femur, when visualized with its characteristic appearance, was recorded. Linear regression analysis with the correlation coefficient of the femur growth-curve (r = 0.989, p less than 0.001) and that of the BPD (r = 0.985, p less than 0.001) showed that the former is as good as the latter. The femur growth-curve from 12 to 40 week's gestation with a mean +/- 2 SD was constructed. Estimation of fetal age by femur length measurement was compared with that assessed by the BPD in a further 54 women. A close correlation was found (r = 0.993, p less than 0.001). Measurement of the fetal femur appears to be a reliable method for assessing gestational age, which can compensate for the limitations of the BPD method.