Neuromotor development in nocturnal enuresis.
In children with nocturnal enuresis, a higher rate of minor neurological dysfunction has been found. The aim of this study was to assess timed performance (a measure of motor performance speed) and associated movements using a standardized and reliable instrument. The motor function of 37 children with nocturnal enuresis (27 males, 10 females; mean age 10y 7mo [SD 1y 10mo]; age range 8y-14y 8mo) and 40 comparison children without enuresis (17 males, 23 females; mean age 10y 7mo [SD 1y 6mo]; age range 8y-14y 8mo) was assessed using the Zurich Neuromotor Assessment. Children with nocturnal enuresis showed a slower motor performance than comparison children, particularly for repetitive hand and finger movements. This study provides evidence for a maturational deficit in motor performance in children with nocturnal enuresis. In addition to a maturational deficit of the brainstem, it is proposed that there is a possible maturational deficit of the motor cortex circuitry and related cortical areas in children with nocturnal enuresis.


The prognostic importance of the ossific nucleus in the treatment of congenital dysplasia of the hip.
Ischemic necrosis of the femoral head occurring after the treatment of congenital dysplasia of the hip can negatively affect the long-term prognosis of the involved hip. Some investigators have suggested that the presence of the ossific nucleus of the femoral head at the time of closed or open reduction is associated with a lower rate of ischemic necrosis. This finding, if verified, could lead to a delay in the treatment of a dislocated hip until ossification of the femoral head has begun, which may be well after the age when the patient has started to walk. We conducted a computerized search of the medical records at our two tertiary-care children's hospitals to identify all patients with congenital dysplasia of the hip who had had a closed or open reduction between January 1, 1979, and December 31, 1993. One hundred and twenty-four patients (153 hips) who satisfied the criteria for inclusion were identified. The ossific nucleus was present in ninety hips and absent in sixty-three. Closed reduction was used in 112 hips and open reduction, in forty-one. Ischemic necrosis was identified in five hips (3 percent): four (6 percent) of the sixty-three hips that did not have an ossific nucleus and one (1 percent) of the ninety hips that had an ossific nucleus at the time of the reduction. With the numbers available for study, we could not detect a difference between these two groups. The age at reduction (p > 0.99), the method of reduction (p = 0.611), previous treatment with a Pavlik harness (p = 0.592), the use of preliminary traction (p = 0.602), concomitant procedures (p > 0.99), and a failure of the primary closed reduction (p = 0.579) were not associated with the development of ischemic necrosis after reduction. In our analysis of patients who were managed over a fifteen-year period, the data did not support the hypothesis that the presence of an ossific nucleus at the time of reduction of a congenitally dislocated hip is associated with a lower prevalence of ischemic necrosis of the femoral head. Sound operative principles dictate that operative reduction of a congenitally displaced hip should be performed when the child can be safely placed under anesthesia and without regard to the presence or absence of the ossific nucleus.


Reproductive performance of women with unicornuate uterus.
The reproductive history of 19 women with a diagnosis of unicornuate uterus confirmed by laparoscopy or laparotomy is analyzed. The patients were followed for 2 to 10 years. One patient had a cavitary communicating rudimentary horn, four a cavitary noncommunicating rudimentary horn, seven a noncavitary rudimentary horn, and seven no rudimentary horn. Six of the patients presented with primary infertility. The other 13 women had a total of 29 pregnancies, 1 (3.4%) in a rudimentary horn determining rupture; abortions occurred in 17 (58.6%), premature labor in 3 (10.3%), and term births in 8 (27.6%), with a live birth rate of 38%. Of the 11 births, 6 (54.5%) were breech presentations, and 9 (81.8%) were cesarean sections. In five cases the rudimentary horn was removed, with associated salpingooophorectomy in three patients. Cervical cerclage was not performed in any of the patients.


Increased autophagy in placentas of intrauterine growth-restricted pregnancies.
Unexplained intrauterine growth restriction (IUGR) may be a consequence of placental insufficiency; however, its etiology is not fully understood. We surmised that defective placentation in IUGR dysregulates cellular bioenergic homeostasis, leading to increased autophagy in the villous trophoblast. The aims of this work were (1) to compare the differences in autophagy, p53 expression, and apoptosis between placentas of women with normal or IUGR pregnancies; (2) to study the effects of hypoxia and the role of p53 in regulating trophoblast autophagy; and (3) to investigate the relationship between autophagy and apoptosis in hypoxic trophoblasts. Compared with normal pregnant women, women with IUGR had higher placental levels of autophagy-related proteins LC3B-II, beclin-1, and damage-regulated autophagy modulator (DRAM), with increased p53 and caspase-cleaved cytokeratin 18 (M30). Furthermore, cytotrophoblasts cultured under hypoxia (2% oxygen) in the presence or absence of nutlin-3 (a p53 activity stimulator) had higher levels of LC3B-II, DRAM, and M30 proteins and increased Bax mRNA expression compared with controls cultured under standard conditions. In contrast, administration of pifithrin-α (a p53 activity inhibitor) during hypoxia resulted in protein levels that were similar to those of the control groups. Moreover, cytotrophoblasts transfected with LC3B, beclin-1, or DRAM siRNA had higher levels of M30 compared with the controls under hypoxia. However, transfection with Bcl-2 or Bax siRNA did not cause any significant change in the levels of LC3B-II in hypoxic cytotrophoblasts. Together, these results suggest that there is a crosstalk between autophagy and apoptosis in IUGR and that p53 plays a pivotal and complex role in regulating trophoblast cell turnover in response to hypoxic stress.


Human CD4+CD25low adaptive T regulatory cells suppress delayed-type hypersensitivity during transplant tolerance.
Adaptive T regulatory (T(R)) cells mediate the suppression of donor-specific, delayed-type hypersensitivity (DTH) in tolerant organ transplant recipients. We hypothesized that cells belonging to the CD4(+)CD25(+) T cell subset but distinct from natural T(R) cells may fulfill this role. To test this hypothesis, PBMC and biopsy samples from two tolerant kidney transplant recipients (K1 and K2) were analyzed. When transferred with recipient APC into a SCID mouse footpad, CD4(+) T cells were hyporesponsive in DTH to donor type HLA-B Ags and derivative allopeptides. However, anti-human TGF-beta1 Ab revealed a response to immunodominant allopeptides in both patients, suggesting that CD4(+) T effector (T(E)) cells coexisted with suppressive, TGF-beta1-producing CD4(+) T(R) cells. During in vitro culture, allopeptide stimulation induced both IFN-gamma-producing and surface TGF-beta1(+) T cells. The relative strength of the latter response in patient K1 was inversely correlated with the level of systemic anti-donor DTH, which varied over a 6-year interval. Allopeptide-induced surface TGF-beta1 expression was found primarily in Forkhead box P3 (FoxP3)-negative CD4(+)CD25(low) T cells, which could adoptively transfer suppression of donor-specific DTH. Biopsy samples contained numerous surface TGF-beta1(+) mononuclear cells that costained for CD4 and, less frequently CD25, but were negative for FoxP3. The CD4(+)TGF-beta1(+) T cells were localized primarily to the tubulointerstitium, whereas TGF-beta1(-)FoxP3(+)CD25(+) cells were found mainly in lymphoid aggregates. Thus, adaptive T(R) cells suppressing T(E) cell responses to donor allopeptides in two tolerant patients appear to be functionally and phenotypically distinct from CD4(+)CD25(high)FoxP3(+) T cells.


Stereo camera based virtual cane system with identifiable distance tactile feedback for the blind.
In this paper, we propose a new haptic-assisted virtual cane system operated by a simple finger pointing gesture. The system is developed by two stages: development of visual information delivery assistant (VIDA) with a stereo camera and adding a tactile feedback interface with dual actuators for guidance and distance feedbacks. In the first stage, user's pointing finger is automatically detected using color and disparity data from stereo images and then a 3D pointing direction of the finger is estimated with its geometric and textural features. Finally, any object within the estimated pointing trajectory in 3D space is detected and the distance is then estimated in real time. For the second stage, identifiable tactile signals are designed through a series of identification experiments, and an identifiable tactile feedback interface is developed and integrated into the VIDA system. Our approach differs in that navigation guidance is provided by a simple finger pointing gesture and tactile distance feedbacks are perfectly identifiable to the blind.


The genome of Borrelia recurrentis, the agent of deadly louse-borne relapsing fever, is a degraded subset of tick-borne Borrelia duttonii.
In an effort to understand how a tick-borne pathogen adapts to the body louse, we sequenced and compared the genomes of the recurrent fever agents Borrelia recurrentis and B. duttonii. The 1,242,163-1,574,910-bp fragmented genomes of B. recurrentis and B. duttonii contain a unique 23-kb linear plasmid. This linear plasmid exhibits a large polyT track within the promoter region of an intact variable large protein gene and a telomere resolvase that is unique to Borrelia. The genome content is characterized by several repeat families, including antigenic lipoproteins. B. recurrentis exhibited a 20.4% genome size reduction and appeared to be a strain of B. duttonii, with a decaying genome, possibly due to the accumulation of genomic errors induced by the loss of recA and mutS. Accompanying this were increases in the number of impaired genes and a reduction in coding capacity, including surface-exposed lipoproteins and putative virulence factors. Analysis of the reconstructed ancestral sequence compared to B. duttonii and B. recurrentis was consistent with the accelerated evolution observed in B. recurrentis. Vector specialization of louse-borne pathogens responsible for major epidemics was associated with rapid genome reduction. The correlation between gene loss and increased virulence of B. recurrentis parallels that of Rickettsia prowazekii, with both species being genomic subsets of less-virulent strains.


BT2, a BTB protein, mediates multiple responses to nutrients, stresses, and hormones in Arabidopsis.
The Arabidopsis (Arabidopsis thaliana) gene BT2 encodes a 41-kD protein that possesses an amino-terminal BTB domain, a central TAZ domain, and a carboxyl-terminal calmodulin-binding domain. We previously demonstrated that BT2 could activate telomerase expression in mature Arabidopsis leaves. Here, we report its distinct role in mediating diverse hormone, stress, and metabolic responses. We serendipitously discovered that steady-state expression of BT2 mRNA was regulated diurnally and controlled by the circadian clock, with maximum expression in the dark. This pattern of expression suggested that BT2 mRNA could be linked to the availability of photosynthate in the plant. Exogenous sugars decreased BT2 expression, whereas exogenous nitrogen increased expression. bt2 loss-of-function mutants displayed a hypersensitive response to both sugar-mediated inhibition of germination and abscisic acid (ABA)-mediated inhibition of germination, thus supporting a role of ABA in sugar signaling in germination and development. Moreover, constitutive expression of BT2 imparted resistance to both sugars and ABA at germination, suggesting that BT2 suppresses sugar and ABA responses. In support of the previously described antagonistic relationship between ABA and auxin, we found that BT2 positively regulated certain auxin responses in plants, as revealed by knocking down BT2 expression in the high-auxin mutant yucca. Accumulation of BT2 mRNA was affected by a variety of hormones, nutrients, and stresses, and BT2 was required for responses to many of these same factors. Together, these results suggest that BT2 is a central component of an interconnected signaling network that detects and responds to multiple inputs.


Evolutionary fuzzy modeling human diagnostic decisions.
Fuzzy CoCo is a methodology, combining fuzzy logic and evolutionary computation, for constructing systems able to accurately predict the outcome of a human decision-making process, while providing an understandable explanation of the underlying reasoning. Fuzzy logic provides a formal framework for constructing systems exhibiting both good numeric performance (accuracy) and linguistic representation (interpretability). However, fuzzy modeling--meaning the construction of fuzzy systems--is an arduous task, demanding the identification of many parameters. To solve it, we use evolutionary computation techniques (specifically cooperative coevolution), which are widely used to search for adequate solutions in complex spaces. We have successfully applied the algorithm to model the decision processes involved in two breast cancer diagnostic problems, the WBCD problem and the Catalonia mammography interpretation problem, obtaining systems both of high performance and high interpretability. For the Catalonia problem, an evolved system was embedded within a Web-based tool-called COBRA-for aiding radiologists in mammography interpretation.


Estrogenic affinity labels: synthesis, irreversible receptor binding, and bioactivity of aziridine-substituted hexestrol derivatives.
To develop an affinity label for the estrogen receptor that would be an estrogen agonist, rather than antagonist, we prepared several aziridine derivatives of the potent nonsteroidal estrogen hexestrol [3R,4S)-3,4-bis(4-hydroxyphenyl)hexane) bearing an aziridine function on the side chain. Three functional groups link the hexestrol ligand and the aziridine: a carbonyl group (ketone or ester), a thioether, or a methylene chain. The apparent competitive binding affinity of these derivatives for the estrogen receptor ranges from 1.8% to 25% that of estradiol, and most of them bind in a time-dependent, irreversible manner with the receptor, although the rate and efficiency of this binding vary widely, often with relatively small changes in structure. This is consistent with the irreversible attachment requiring a precise alignment of activating and reacting residues in the binding site of the receptor. The estrogenic and antiestrogenic activity of these aziridine derivatives was investigated in MCF-7 human breast cancer cells. Most of the compounds are agonists, with one being an antagonist. The derivative (6R,7S)-1-N-aziridinyl-6,7-bis(4-hydroxyphenyl)-5-nonanone (keto-nonestrol aziridine 3) appears to have the most ideal behavior of the estrogenic affinity labeling agents prepared: It is an agonist, and it binds to receptor irreversibly, efficiently, and quite rapidly.


Trends and disparities in referral to cardiac rehabilitation after percutaneous coronary intervention.
Despite the known benefits of cardiac rehabilitation in patients with coronary artery disease, referral rates to rehabilitation programs remain low. We determined the incidence and determinants of cardiac rehabilitation referral rates for patients undergoing percutaneous coronary intervention (PCI). The incidence and predictors of referral to cardiac rehabilitation were assessed among 145,661 consecutive patients undergoing PCI and surviving to hospital discharge across 31 hospitals in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium between 2003 and 2008. The 6-year cardiac rehabilitation referral rate was 60.2%. Younger age, male gender, white race, and presentation with acute or severe disease (ie, acute myocardial infarction [AMI] in the previous 24 hours and ST-elevation myocardial infarction) were associated with increased referral to rehabilitation (all P < .0001). Most medical comorbidities were associated with decreased referral. Referral rates for cardiac rehabilitation were below the rates of other AMI quality-of-care indicators and more variable across hospital sites. Race-specific referral rates differed significantly in the lowest referring hospitals (P < .0001) but not in the highest referring hospitals (P = .16). Women had a 0.7% relative decrease in referral as compared to men (P = .0188) in the highest referring hospitals but a 26.7% relative decrease in referral in the lowest referring hospitals (P = .02). Over one third of patients undergoing PCI are not referred for cardiac rehabilitation. Referral rates are below the rates of other AMI quality-of-care performance measures and more variable across sites. Racial and gender disparities in referral to rehabilitation exist but are concentrated at the lowest referring hospitals.


Characterization of Helicobacter pylori VacA-containing vacuoles (VCVs), VacA intracellular trafficking and interference with calcium signalling in T lymphocytes.
The human pathogen Helicobacter pylori colonizes half of the global population. Residing at the stomach epithelium, it contributes to the development of diseases such as gastritis, duodenal and gastric ulcers, and gastric cancer. A major factor is the secreted vacuolating toxin VacA, which forms anion-selective channels in the endosome membrane that cause the compartment to swell, but the composition and purpose of the resulting VacA-containing vacuoles (VCVs) are still unknown. VacA exerts influence on the host immune response in various ways, including inhibition of T-cell activation and proliferation and suppression of the host immune response. In this study, for the first time the composition of VCVs from T cells was comprehensively analysed to investigate VCV function. VCVs were successfully isolated via immunomagnetic separation, and the purified vacuoles were analysed by mass spectrometry. We detected a set of 122 VCV-specific proteins implicated among others in immune response, cell death and cellular signalling processes, all of which VacA is known to influence. One of the individual proteins studied further was stromal interaction molecule (STIM1), a calcium sensor residing in the endoplasmic reticulum (ER) that is important in store-operated calcium entry. Live cell imaging microscopy data demonstrated colocalization of VacA with STIM1 in the ER and indicated that VacA may interfere with the movement of STIM1 towards the plasma membrane-localized calcium release activated calcium channel protein ORAI1 in response to Ca(2+) store depletion. Furthermore, VacA inhibited the increase of cytosolic-free Ca(2+) in the Jurkat E6-1 T-cell line and human CD4(+) T cells. The presence of VacA in the ER and its trafficking to the Golgi apparatus was confirmed in HeLa cells, identifying these two cellular compartments as novel VacA target structures.


Analysis of the T cell receptor V beta repertoire in 2,4,6-trinitrobenzenesulfonic acid induced colitis in mice.
The aim of this study was to analyze which types of T cells are at work and the specific nature of their response, using a mouse 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis model. The response of T cells to TNBS was analyzed by anti-TNBS mixed-lymphocyte reaction. T cell clones were established by limiting dilution. Phenotypes and T cell receptor (TCR) V beta of T cells were analyzed by flow cytometry. Colitis was induced by administration of TNBS enemas, and lamina propria lymphocytes were isolated and analyzed. The proliferative responses to TNBS of spleen T cells were partially inhibited by the addition of antimouse CD4 or CD8 antibodies to the mixed-lymphocyte culture. Conversely, these were inhibited by the addition of both antibodies. Flow cytometric analysis showed that TCR V beta 14 T cells specifically increased in the CD8+ T cell population. We established CD8+ TCR V beta 14 T cell clones which were TNBS reactive and self-restricted. Investigation using lamina propria lymphocytes in TNBS-induced colitis revealed that the rate of CD8+ TCR V beta 14 T cells changed with histological inflammatory activity which also attained a peak on day 5 following enema administration. Both CD4+ and CD8+ T cell subsets responded to TNBS, and the rate of CD8+ TCR V beta 14 T cells changed with histological inflammatory activity in TNBS-induced colitis.


Intra-articular corticosteroid injections in the foot and ankle: a prospective 1-year follow-up investigation.
Most evidence for the efficacy of intra-articular corticosteroids is confined to the knee, with few studies considering the joints of the foot and ankle. The aim of this study was to identify the long-term efficacy of corticosteroid injection in foot and ankle joints. All patients undergoing intra-articular corticosteroid injections into foot and ankle joints over a 10-month period were recruited into the study. Patients were asked to complete a foot-related quality of life questionnaire, namely the Foot and Ankle Outcome Score, immediately before intra-articular injection and at set points up to 1-year afterward. Eighteen patients, comprising 36 foot and ankle joints, were recruited into the study. There was a statistically significant score improvement following corticosteroid injection up to and including 6 months postinjection. No independent clinical factors were identified that could predict a better postinjection response. The magnitude of the response at 2 months was found to predict a sustained response at 9 months and 1 year. Intra-articular corticosteroids improved symptom scores in patients with foot and ankle arthritis. The duration of this response was varied and patient factors affecting the response remain unclear. Response to the injection at 2 months can be used to predict the duration of beneficial effects up to at least 1 year. 2.


Renal escape from vasopressin: role of pressure diuresis.
This study was designed to examine the role of increased renal artery pressure (RAP) in mediating escape from the antidiuretic action of vasopressin (AVP). In six conscious dogs in which RAP was permitted to increase, AVP infusion, at a rate (0.2 mU X kg-1 X mm-1 iv) that was acutely subpressor, gradually raised mean arterial pressure (MAP) from 97 +/- 2 to 126 +/- 4 mmHg after 5 days while decreasing urine volume and increasing urine osmolality. However, after 4-5 days of AVP infusion, urine volume and osmolality returned to control, and the hypertensive effect of AVP waned so that after 9 days of AVP, MAP averaged only 113 +/- 5 mmHg. In contrast, when RAP was prevented from increasing in seven dogs with a servo-controlled aortic occluder, AVP caused sustained decreases in urine volume and elevated urine osmolality from 609 +/- 27 to 1,160-1,711 mosmol/kg H2O throughout 8 days of infusion. The hypertensive effect of AVP did not wane when RAP was servo-controlled, and after 8 days of AVP infusion, MAP averaged 152 +/- 7 mmHg, compared with a control of 96 +/- 2 mmHg. Servo-controlling RAP also prevented the marked sodium and chloride losses seen with chronic AVP infusion in normal dogs. These findings indicate that escape from the antidiuretic action of AVP is mediated by increased RAP, which causes diuresis and natriuresis, thereby diminishing the hypertensive effect of AVP. However, when pressure diuresis and natriuresis are prevented, AVP causes severe chronic hypertensive, suggesting that AVP could be an important hypertensive mechanism when renal function is impaired.


Exercise-associated amenorrhea, low bone density, and estrogen replacement therapy.
Women with exercise-associated amenorrhea have a higher frequency of osteoporosis than eumenorrheic runners and sedentary women. The use of hormone replacement therapy was suggested many years ago to increase bone density in exercising women with amenorrhea and low bone density. To determine if hormone replacement therapy increased bone density in women with exercise-associated amenorrhea. We performed a retrospective clinical study comparing the changes in bone density in 8 women runners who took hormone replacement therapy with 5 who refused medication but who were followed up as controls over 24 to 30 months. Vertebral and femoral neck bone density significantly increased by 8.0% +/- 1.2% (+/- SEM) and 4.1% +/- 0.3% (+/- SEM), respectively, in 8 women runners with amenorrhea taking 24 to 30 months of estrogen replacement therapy with progestational support. Control women not taking replacement therapy had nonsignificant decreases of less than 2.5% at each site. Hormone replacement therapy appears to increase bone density in amenorrheic runners.


Activation of a membrane-associated androgen receptor promotes cell death in primary cortical astrocytes.
In the central nervous system, androgens can exert either protective or damage-promoting effects. For example, testosterone protects neurons against beta-amyloid toxicity, whereas in other studies, testosterone exacerbated stroke-induced lesion size. The mechanism underlying this duality of androgens is still unclear. Recently, our laboratory reported that androgens elicit opposite effects on the ERK/MAPK and Akt signaling pathways, depending on whether a membrane androgen receptor (AR) or intracellular AR was activated. By extension, we hypothesized that androgens may affect cell viability differently depending on which receptor is activated. Here, we found that dihydrotestosterone (DHT) protected primary cortical astrocytes from the metabolic and oxidative insult associated with iodoacetic acid-induced toxicity, whereas DHT-BSA, a cell impermeable analog of DHT that preferentially targets the membrane AR, suppressed Akt signaling, increased caspase 3/7 activity, and enhanced iodoacetic acid-induced cell death. Interestingly, DHT-BSA also blocked the protective effects of DHT and estradiol. Collectively, these data support the existence of two, potentially competing, pathways for androgens in a given cell or tissue that may provide insight into the controversy of whether androgen therapy is beneficial or detrimental.


Genetic consequences of introducing allopatric lineages of Bluestriped Snapper (Lutjanus kasmira) to Hawaii.
A half century ago the State of Hawaii began a remarkable, if unintentional, experiment on the population genetics of introduced species, by releasing 2431 Bluestriped Snappers (Lutjanus kasmira) from the Marquesas Islands in 1958 and 728 conspecifics from the Society Islands in 1961. By 1992 L. kasmira had spread across the entire archipelago, including locations 2000 km from the release site. Genetic surveys of the source populations reveal diagnostic differences in the mtDNA control region (d = 3.8%; phi(ST) = 0.734, P < 0.001) and significant allele frequency differences at nuclear DNA loci (F(ST) = 0.49; P < 0.001). These findings, which indicate that source populations have been isolated for approximately half a million years, set the stage for a survey of the Hawaiian Archipelago (N = 385) to determine the success of these introductions in terms of genetic diversity and breeding behaviour. Both Marquesas and Society mtDNA lineages were detected at each survey site across the Hawaiian Archipelago, at about the same proportion or slightly less than the original 3.4:1 introduction ratio. Nuclear allele frequencies and parentage tests demonstrate that the two source populations are freely interbreeding. The introduction of 2431 Marquesan founders produced only a slight reduction in mtDNA diversity (17%), while the 728 Society founders produced a greater reduction in haplotype diversity (41%). We find no evidence of genetic bottlenecks between islands of the Hawaiian Archipelago, as expected under a stepping-stone model of colonization, from the initial introduction site. This species rapidly colonized across 2000 km without loss of genetic diversity, illustrating the consequences of introducing highly dispersive marine species.


Experience with Tissue Bank Services in 2014 and 2020 in Turku, Finland.
The objective of a musculoskeletal tissue bank is to collect, test, store, and provide musculoskeletal tissue allografts required in orthopedic procedures. Strict exclusion criteria are followed when selecting suitable cadaver musculoskeletal tissue donors, and the allografts are procured under sterile conditions to avoid bacterial contamination. Tissue banking in Turku, Finland, began in 1972, and tissue bank services were last reviewed in 2003. This study aimed to review the operation of the musculoskeletal tissue bank in Turku, Finland, between 2014 and 2020 and to analyze the number, types, and contamination rate of the allografts procured from the cadaver donors. Potential donor-related factors causing bacterial contamination of the allografts and whether potential musculoskeletal tissue donors were overlooked among multiorgan donors were also studied. A retrospective review of all cadaver musculoskeletal tissue donors used in the Hospital District of Southwest Finland Tyks Orto Musculoskeletal Tissue Bank during the study period was conducted, and data on the procured allograft was collected and presented. The donors were selected among patients treated in the intensive care unit (ICU) of Turku University Hospital (TYKS). A total of 28 cadaver donors were used, and 636 allografts were procured between 2014 and 2020. The bacterial contamination rate was 2.5%, which was lower than that in the previous international literature. The median treatment time in the ICU was significantly longer, and the median value of the highest C-reactive protein level was significantly higher in the group of donors with positive allograft bacterial cultures. The bacterial contamination rate in the tissue bank was low on an international scale. Some suitable musculoskeletal tissue donors were overlooked among multiorgan donors.


Comparison between two devices for measuring hip joint motions.
To compare the reliability of measurements of hip motions obtained with two instruments, an electronic inclinometer and a two-arm goniometer, and to investigate whether the two instruments, and different body positions, produce the same measurement data. Maximal active and passive hip movements were measured simultaneously with both instruments, in nine subjects during 10 consecutive measurements at short intervals. Intra-observer variability was lower with the inclinometer in measurements of passive hip rotations. The two instruments showed equal intra-observer variability for hip movements in general. The inclinometer showed lower inter-observer variability in the measurements of active internal rotation. More rotational movement was measured with the two-arm goniometer; more extension and flexion with the inclinometer. Also, more rotational movement was found in the prone position compared to sitting and supine positions. The inclinometer is more reliable in measurements of hip rotation. For hip movements in general the two-arm goniometer is just as accurate when used by only one observer. The two instruments, and some positions, are not interchangeable during consecutive measurements.


Effect of sidestream tobacco smoke components on alpha/beta interferon production.
Mouse embryo fibroblast cell cultures were treated with chemicals that are major components of sidestream (passive) cigarette smoke. These components were 4-aminobiphenyl and aniline-HCl. The cultures produced severely reduced levels of alpha/beta interferon after challenge with polyriboinosinic-polyribocytidylic acid when compared to control cultures. Treatment of additional cell cultures with 2-methylquinoline, and intermediate-level component of sidestream tobacco smoke, or hydrazine-sulfate, a minor component of sidestream tobacco smoke but a major component of mainstream (active) tobacco smoke, also resulted in inhibition of interferon induction with polyriboinosinic acid-polyribocytidylic acid. Therefore, treatment of the cell cultures with chemicals that are carcinogenic was equally effective in inhibiting alpha/beta interferon induction without regard to the sidestream or mainstream smoke origin of the chemical.


Alterations of pulsation absorber characteristics in experimental hydrocephalus.
Analysis of waveform data in previous studies suggests that the pulsatile movement of CSF may play a role in attenuating strong arterial pulsations entering the cranium, and its effectiveness in attenuating these pulsations may be altered by changes in intracranial pressure (ICP). These findings were obtained in studies performed in canines with normal anatomy of the CSF spaces. How then would pulsation absorbance respond to changes in CSF movement under obstructive conditions such as the development of hydrocephalus? In the present study, chronic obstructive hydrocephalus was induced by the injection of cyanoacrylate gel into the fourth ventricle of canines, and pulsation absorbance was compared before and after hydrocephalus induction. Five animals were evaluated with simultaneous recordings of ICP and arterial blood pressure (ABP) before and at 4 and 12 weeks after fourth ventricle obstruction by cyanoacrylate. To assess how the intracranial system responds to the arterial pulsatile component, ABP and ICP waveforms recorded in a time domain had to be analyzed in a frequency domain. In an earlier study the authors introduced a particular technique that allows characterization of the intracranial system in the frequency domain with sufficient accuracy and efficiency. This same method was used to analyze the relationship between ABP and ICP waveforms recorded during several acute states including hyperventilation as well as CSF withdrawal and infusion under conditions before and after inducing chronic obstructive hydrocephalus. Such a relationship is reflected in terms of a gain, which is a function of frequency. The cardiac pulsation absorbance (CPA) index, which is simply derived from a gain evaluated at the cardiac frequency, was used to quantitatively evaluate the changes in pulsation absorber function associated with the development of hydrocephalus within each of the animals, which did become hydrocephalic. To account for normal and hydrocephalic conditions within the same animal and at multiple time points, statistical analysis was performed by repeated-measures ANOVA. The performance of the pulsation absorber as assessed by CPA significantly deteriorated after the development of chronic hydrocephalus. In these animals the decrement in CPA was far more significant than other anticipated changes including those in ICP, compliance, or ICP pulse amplitude. To the extent that the free CSF movement acts as a buffer of arterial pulsation input to flow in microvessels, alterations in the pulsation absorber may play a pathophysiological role. One measure of alterations in the way the brain deals with pulsatile input-the CPA measurement-changes dramatically with the imposition of hydrocephalus. Results in the present study suggest that CPA may serve as a complementary metric to the conventional static measure of intracranial compliance in other experimental and clinical studies.


Classical risk factors for primary coronary artery disease from an aging perspective through Mendelian Randomization.
The significance of classical risk factors in coronary artery disease (CAD) remains unclear in older age due to possible changes in underlying disease pathologies. Therefore, we conducted Mendelian Randomization approaches to investigate the causal relationship between classical risk factors and primary CAD in different age groups. A Mendelian Randomization study was conducted in European-ethnicity individuals from the UK Biobank population. Analyses were performed using data of 22,313 CAD cases (71.6% men) and 407,920 controls (44.5% men). Using logistic regression analyses, we investigated the associations between standardized genetic risk score and primary CAD stratified by age of diagnosis. In addition, feature importance and model accuracy were assessed in different age groups to evaluate predictive power of the genetic risk scores with increasing age. We found age-dependent associations for all classical CAD risk factors. Notably, body mass index (OR 1.22 diagnosis < 50 years; OR 1.02 diagnosis > 70 years), blood pressure (OR 1.12 < 50 years; OR 1.04 > 70 years), LDL cholesterol (OR 1.16 < 50 years; OR 1.02 > 70 years), and triglyceride levels (OR 1.11 < 50 years; 1.04 > 70 years). In line with the Mendelian Randomization analyses, model accuracy and feature importance of the classical risk factors decreased with increasing age of diagnosis. Causal determinants for primary CAD are age dependent with classical CAD risk factors attenuating in relation with primary CAD with increasing age. These results question the need for (some) currently applied cardiovascular disease risk reducing interventions at older age.


Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge augmentation with anorganic bovine bone.
Bone augmentation with the titanium-mesh (Ti-mesh) technique is susceptible to a large rate of complications such as morbidity of bone graft donor site, and mesh exposure to the oral cavity. The purpose of this study was to evaluate the effectiveness of anorganic bovine bone (ABB) in alveolar bone augmentation with the Ti-mesh technique. In addition, we investigated the effect of platelet-rich plasma (PRP) in preventing mesh exposure by using it to cover the Ti-mesh. Patients included in the clinical trial were randomly allocated by a blinded assistant into two groups. The 30 patients recruited for this study underwent 43 alveolar bone augmentation with the Ti-mesh technique using ABB as graft material in all of them. In 15 patients, the Ti-meshes were covered with PRP (PRP group) whereas in the other 15 the Ti-meshes were not (control group). After 6 months, patients were called for clinical, radiographic, and histological evaluation, and implant placement surgery. A total of 97 implants were placed in the augmented bone and their evolution was followed up for a period of 24 months. Significant differences were found between the two study groups in terms of complications and bone formation. In the control group, 28.5% of the cases suffered from mesh exposure, while in the PRP group, no exposures were registered. Radiographic analysis revealed that bone augmentation was higher in the PRP group than in the control group. Overall, 97.3% of implants placed in the control group and 100% of those placed in the PRP group were successful during the monitoring period. We suggest that the positive effect of PRP on the Ti-mesh technique is due to its capacity to improve soft tissue healing, thereby protecting the mesh and graft material secured beneath the gingival tissues. Alveolar bone augmentation using ABB alone in the Ti-mesh technique is sufficient for implant rehabilitation. Besides, covering the Ti-meshes with PRP was a determining factor in avoiding mesh exposure. Ti-mesh exposure provoked significant bone loss, but in most cases it did not affect the subsequent placement of implants.


Quantitative dosimetric verification of an IMRT planning and delivery system.
The accuracy of dose calculation and delivery of a commercial serial tomotherapy treatment planning and delivery system (Peacock. NOMOS Corporation) was experimentally determined. External beam fluence distributions were optimized and delivered to test treatment plan target volumes, including three with cylindrical targets with diameters ranging from 2.0 to 6.2 cm and lengths of 0.9 through 4.8 cm, one using three cylindrical targets and two using C-shaped targets surrounding a critical structure, each with different dose distribution optimization criteria. Computer overlays of film-measured and calculated planar dose distributions were used to assess the dose calculation and delivery spatial accuracy. A 0.125 cm3 ionization chamber was used to conduct absolute point dosimetry verification. Thermoluminescent dosimetry chips, a small-volume ionization chamber and radiochromic film were used as independent checks of the ion chamber measurements. Spatial localization accuracy was found to be better than +/-2.0 mm in the transverse axes (with one exception of 3.0 mm) and +/-1.5 mm in the longitudinal axis. Dosimetric verification using single slice delivery versions of the plans showed that the relative dose distribution was accurate to +/-2% within and outside the target volumes (in high dose and low dose gradient regions) with a mean and standard deviation for all points of -0.05% and 1.1%, respectively. The absolute dose per monitor unit was found to vary by +/-3.5% of the mean value due to the lack of consideration for leakage radiation and the limited scattered radiation integration in the dose calculation algorithm. To deliver the prescribed dose, adjustment of the monitor units by the measured ratio would be required. The treatment planning and delivery system offered suitably accurate spatial registration and dose delivery of serial tomotherapy generated dose distributions. The quantitative dose comparisons were made as far as possible from abutment regions and examination of the dosimetry of these regions will also be important. Because of the variability in the dose per monitor unit and the complex nature of the calculation and delivery of serial tomotherapy, patient-specific quality assurance procedures will include a measurement of the delivered target dose.


Multidisciplinary strategies to treat severe hypoglycemia in hospitalized patients with diabetes mellitus reduce inpatient mortality rate: Experience from an academic community hospital.
Severe hypoglycemia (blood glucose < 50 mg/dl) in hospitalized patients with diabetes mellitus is associated with poor outcomes such as increased mortality and readmission rates. We study the effects of system based interventions in managing severe hypoglycemia and its impact on outcomes. We performed retrospective review of pre- and post- intervention study to quantify severe hypoglycemia in patients admitted in the general internal medicine wards with primary or secondary diagnosis of diabetes mellitus based on ICD-9 and ICD-10 codes. We implemented multidisciplinary interventions including standardization of treatment, education of in-patient medical teams and physician notification and feedback immediately after severe hypoglycemia. The endpoints were the comparative analysis of incidence of severe hypoglycemia, in-patient mortality rate, 30-day mortality rate, 30-day readmission rate, recovery time from hypoglycemia, time to next glucose measurements, use of standardized treatment and physician notification rate pre-and post-intervention. The incidence of severe hypoglycemia per patient with diabetes was reduced from 9.6% (233/2416) to 5.6% (202/3607) (p<0.001) post-intervention. The in-patient mortality rate in patients with severe hypoglycemia reduced from 4.1% to 0% (p = 0.019), 30-day mortality rate reduced from 9.8% to 3.8% (p = 0.058) post-intervention. 30-day readmission rate was comparable between pre-intervention (31.7%) and post-intervention (29%) (p = 0.60). In comparison, the mortality and readmission rates of all diabetic patients did not reduce during the same observation periods. Recovery time reduced from 116 (83-161) to 75 (57-102) min (p<0.01), time to next glucose measurement reduced from 39.5 (34-48) to 32 (28-35) min (p<0.01), use of standardized treatment improved from 22.7% (53/233) to 72.2% (146/202) (p<0.001) and physician notification rate increased from 29.2 (68/233) to 84.7% (171/202) post-intervention. Our study shows that multidisciplinary strategies improves the process of early detection and management of severe hypoglycemia and reduce incidence and in-patient mortality rate.


Myxococcus xanthus swarms are driven by growth and regulated by a pacemaker.
The principal social activity of Myxococcus xanthus is to organize a dynamic multicellular structure, known as a swarm. Although its cell density is high, the swarm can grow and expand rapidly. Within the swarm, the individual rod-shaped cells are constantly moving, transiently interacting with one another, and independently reversing their gliding direction. Periodic reversal is, in fact, essential for creating a swarm, and the reversal frequency controls the rate of swarm expansion. Chemotaxis toward nutrient has been thought to drive swarming, but here the nature of swarm growth and the impact of genetic deletions of members of the Frz family of proteins suggest otherwise. We find that three cytoplasmic Frz proteins, FrzCD, FrzF, and FrzE, constitute a cyclic pathway that sets the reversal frequency. Within each cell these three proteins appear to be connected in a negative-feedback loop that produces oscillations whose frequencies are finely tuned by methylation and by phosphorylation. This oscillator, in turn, drives MglAB, a small G-protein switch, to oscillate between its GTP- and GDP-bound states that ultimately determine when the cell moves forward or backward. The periodic reversal of interacting rod-shaped cells promotes their alignment. Swarm organization ensures that each cell can move without blocking the movement of others.


Detecting asthma and bronchial hyperresponsiveness in children.
The prevalence of asthma in children is increasing worldwide. Although the features of asthma are well documented, defining asthma remains a problem. The clinical definition of asthma does not take into account the concept of airway inflammation. A broader definition that incorporates the inflammatory process, reversibility of airway obstruction, and airway responsiveness needs to be more widely adopted. Bronchial hyperresponsiveness is one of the key features in asthma and it can be documented by using pharmacological or non-pharmacological means. The latter appears to be a more physiological test and more acceptable to children. This article gives an overview of the features of asthma and bronchial hyperresponsiveness and shows how various non-pharmacological bronchial challenge tests can help identify bronchial hyperresponsiveness and thus help diagnose asthma in children.


Quantifying ruminal nitrogen metabolism using the omasal sampling technique in cattle--a meta-analysis.
Mixed model analysis of data from 32 studies (122 diets) was used to evaluate the precision and accuracy of the omasal sampling technique for quantifying ruminal-N metabolism and to assess the relationships between nonammonia-N flow at the omasal canal and milk protein yield. Data were derived from experiments in cattle fed North American diets (n=36) based on alfalfa silage, corn silage, and corn grain and Northern European diets (n=86) composed of grass silage and barley-based concentrates. In all studies, digesta flow was quantified using a triple-marker approach. Linear regressions were used to predict microbial-N flow to the omasum from intake of dry matter (DM), organic matter (OM), or total digestible nutrients. Efficiency of microbial-N synthesis increased with DM intake and there were trends for increased efficiency with elevated dietary concentrations of crude protein (CP) and rumen-degraded protein (RDP) but these effects were small. Regression of omasal rumen-undegraded protein (RUP) flow on CP intake indicated that an average 32% of dietary CP escaped and 68% was degraded in the rumen. The slope from regression of observed omasal flows of RUP on flows predicted by the National Research Council (2001) model indicated that NRC predicted greater RUP supply. Measured microbial-N flow was, on average, 26% greater than that predicted by the NRC model. Zero ruminal N-balance (omasal CP flow=CP intake) was obtained at dietary CP and RDP concentrations of 147 and 106 g/kg of DM, corresponding to ruminal ammonia-N and milk urea N concentrations of 7.1 and 8.3mg/100mL, respectively. Milk protein yield was positively related to the efficiency of microbial-N synthesis and measured RUP concentration. Improved efficiency of microbial-N synthesis and reduced ruminal CP degradability were positively associated with efficiency of capture of dietary N as milk N. In conclusion, the results of this study indicate that the omasal sampling technique yields valuable estimates of RDP, RUP, and ruminal microbial protein supply in cattle.


Effects of retraction force and anchorage reinforcement on occlusal force: a model study.
The aim of this study was to investigate the effects of retraction force and anchorage reinforcement with orthodontic mini implants on occlusal force. A strain gauge was attached to the palatal surface of the maxillary right first molar on an en masse retraction model. Occlusal forces were measured from this model, according to different retraction forces that were generated by elastic chain, under varied compressive forces (simulating masticatory forces). This retraction experiment was then performed again, after using anchorage reinforcement with an orthodontic mini implant. Occlusal force decreased as retraction force increased. The decrease showed a significant difference above 150g of retraction force (P < 0.05) and was more definite under compressive force higher than 150 N (P < 0.001). After anchorage reinforcement with the orthodontic mini implant, however, occlusal force did not significantly decrease with increasing retraction force. Significant differences in occlusal force were noted between the conditions with and without anchorage reinforcement when the applied retraction force was greater than 200g. Occlusal force tends to decrease during retraction, and this decrease can be prevented by anchorage reinforcement with orthodontic mini implants. Further investigation on the actual masticatory process in humans is required for more clear clinical implication.


Understanding cellular glycan surfaces in the central nervous system.
Glycosylation, the enzymatic process by which glycans are attached to proteins and lipids, is the most abundant and functionally important type of post-translational modification associated with brain development, neurodegenerative disorders, psychopathologies and brain cancers. Glycan structures are diverse and complex; however, they have been detected and targeted in the central nervous system (CNS) by various immunohistochemical detection methods using glycan-binding proteins such as anti-glycan antibodies or lectins and/or characterized with analytical techniques such as chromatography and mass spectrometry. The glycan structures on glycoproteins and glycolipids expressed in neural stem cells play key roles in neural development, biological processes and CNS maintenance, such as cell adhesion, signal transduction, molecular trafficking and differentiation. This brief review will highlight some of the important findings on differential glycan expression across stages of CNS cell differentiation and in pathological disorders and diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, schizophrenia and brain cancer.


Visual analogue scales: How can we interpret them in experimental studies of irritation in the eyes, nose, throat and airways?
The aim of this study was to investigate if visual analogue scales (VAS) of objective symptoms could be validated against objective measurements in exposure studies of chemical vapours in humans. This validation comprises the results of symptom ratings of irritation and objective measurements of effects of the eye, nose and throat from studies of nine different chemicals. The objective measurements included blinking frequency as a measure of eye irritation, acoustic rhinometry of nose irritation and the lung function parameter FEV₁ of irritation in the throat and airways. The statistical analyses were performed with logistic quantile regression. The results show no overall clear correlation between symptom ratings of irritation and objective measurements, although some statistically significant association was found. The last rating of eye irritation during the exposure was significantly correlated at the 75th percentile to the change in blinking frequency during exposure compared with before (P = 0.013). There was also a significant association between ratings of discomfort in the nose and decrease of the minimal nasal cross-sectional area at the 75th percentile (P = 0.016). Further, a nonsignificant association between ratings of discomfort in the nose and decrease in nasal volume was found. No correlation between FEV₁ and ratings of discomfort in the throat or breathing difficulty was detected. There is a relationship between subjective symptoms and objective measures regarding eye and nose irritation at low chemical exposure levels. Thus, the results of this investigation support the use of VAS in chamber exposure studies and could consequently be expanded into field studies.


A common regulatory locus affects both HNF4/HNF1alpha pathway activation and sensitivity to LPS-mediated apoptosis in rat hepatoma cells.
Lipopolysaccharide (LPS) has been shown to protect certain cultured mammalian cells from undergoing programmed cell death (apoptosis) when exposed to tumor necrosis factor (TNF). However, LPS has also been reported to induce apoptosis in cultured endothelial cells, suggesting that apoptotic response mechanisms may be dependent upon cell type. In order to understand the influence of tissue-specific gene expression on apoptosis, we compared LPS-induced apoptosis in hepatoma cells with dedifferentiated hepatoma variant cells that have been selected for the loss of the liver-enriched HNF4/HNF1alpha transcriptional activation pathway. We report here that while human, rat and mouse hepatoma cell lines are resistant to LPS-mediated cell death, the HNF4-/HNF1alpha- rat hepatoma variant cells undergo rapid apoptosis (as determined by morphological analysis, DNA laddering and the TUNEL assay) upon exposure to LPS. Genetic rescue experiments show that restoration of the HNF4/HNF1alpha pathway via chromosome transfer render the hepatoma variant cells resistant to LPS-mediated apoptosis. However, the introduction of HNF1alpha alone failed to alter the apoptotic phenotype, suggesting that the defect(s) in the hepatoma variant cells that influence apoptotic responses lies upstream of HNF4/HNF1alpha expression. This study provides for the first time direct evidence of a common regulatory locus involved in activation of hepatic gene expression and sensitivity to LPS-mediated apoptosis.


The two-component system WalKR provides an essential link between cell wall homeostasis and DNA replication in Staphylococcus aureus.
Among the 16 two-component systems in the opportunistic human pathogen Staphylococcus aureus, only WalKR is essential. Like the orthologous systems in other Bacillota, S. aureus WalKR controls autolysins involved in peptidoglycan remodeling and is therefore intimately involved in cell division. However, despite the importance of WalKR in S. aureus, the basis for its essentiality is not understood and the regulon is poorly defined. Here, we defined a consensus WalR DNA-binding motif and the direct WalKR regulon by using functional genomics, including chromatin immunoprecipitation sequencing, with a panel of isogenic walKR mutants that had a spectrum of altered activities. Consistent with prior findings, the direct regulon includes multiple autolysin genes. However, this work also revealed that WalR directly regulates at least five essential genes involved in lipoteichoic acid synthesis (ltaS): translation (rplK), DNA compaction (hup), initiation of DNA replication (dnaA, hup) and purine nucleotide metabolism (prs). Thus, WalKR in S. aureus serves as a polyfunctional regulator that contributes to fundamental control over critical cell processes by coordinately linking cell wall homeostasis with purine biosynthesis, protein biosynthesis, and DNA replication. Our findings further address the essentiality of this locus and highlight the importance of WalKR as a bona fide target for novel anti-staphylococcal therapeutics. IMPORTANCE The opportunistic human pathogen Staphylococcus aureus uses an array of protein sensing systems called two-component systems (TCS) to sense environmental signals and adapt its physiology in response by regulating different genes. This sensory network is key to S. aureus versatility and success as a pathogen. Here, we reveal for the first time the full extent of the regulatory network of WalKR, the only staphylococcal TCS that is indispensable for survival under laboratory conditions. We found that WalKR is a master regulator of cell growth, coordinating the expression of genes from multiple, fundamental S. aureus cellular processes, including those involved in maintaining cell wall metabolism, protein biosynthesis, nucleotide metabolism, and the initiation of DNA replication.


Tumor uptake of the RGD dimeric probe (99m)Tc-G3-2P4-RGD2 is correlated with integrin αvβ3 expressed on both tumor cells and neovasculature.
Integrin αvβ3 has been well-documented as one of the key players in the process of tumor angiogenesis. Radiolabeled RGD (Arg-Gly-Asp) peptides that specifically target integrin αvβ3 have great potential for tumor early detection and noninvasively monitoring the status of tumor angiogenesis. We developed a cyclic RGD dimeric probe (99m)Tc-HYNIC-Gly3-E[PEG4-c(RGDfK)]2 ((99m)Tc-G3-2P4-RGD2) (using tricine and TPPTS as the coligands, TPPTS = trisodium triphenylphosphine-3,3',3''-trisulfonate), and investigated whether it could be used to noninvasively visualize and quantify integrin αvβ3 expression in vivo. HYNIC-Gly3-E[PEG4-c(RGDfK)]2 was synthesized and labeled with (99m)Tc. The biodistribution and planar γ-imaging studies of (99m)Tc-G3-2P4-RGD2 were performed in both U87MG (human integrin αvβ3 positive/murine integrin αvβ3 positive) and HT-29 (human integrin αvβ3 negligible /murine integrin αvβ3 positive) tumor-bearing nude mouse models. The correlation of (99m)Tc-G3-2P4-RGD2 tumor uptake values (measured by ex vivo biodistribution) with expression levels of human integrin αvβ3 or murine integrin αvβ3 (measured by Western blot) were determined in U87MG and HT-29 tumor models, respectively. (99m)Tc-G3-2P4-RGD2 exhibited increased receptor binding affinity and in vivo tumor uptake as compared with previously reported RGD dimeric tracer (99m)Tc-RGD2 (without Gly3 and PEG4 spacers). The tumor uptake of (99m)Tc-G3-2P4-RGD2 was related to the expression levels of both human integrin αvβ3 (expressed on tumor cells) and murine integrin αvβ3 (expressed on newborn tumor vasculature). Our results demonstrate that (99m)Tc-G3-2P4-RGD2 is a useful agent for integrin αvβ3 imaging. The relationship between (99m)Tc-G3-2P4-RGD2 uptake and integrin αvβ3 expression level as determined by this study would provide useful information for clinical translation of RGD probes.


Enrichment of naturally occurring radionuclides and trace elements in Yatagan and Yenikoy coal-fired thermal power plants, Turkey.
Coal, residues and waste produced by the combustion of the coal contain naturally occurring radionuclides such as 238U, 226Ra, 210Pb, 232Th and 40K and trace elements such as Cd, Cr, Pb, Ni and Zn. In this work, coal and its combustion residues collected from Yatagan and Yenikoy coal fired thermal power plants (CPPs) in Turkey were studied to determine the concentrations of natural radionuclides and trace elements, and their enrichments factors to better understand the radionuclide concentration processes within the combustion system. In addition, the utilization of coal fly ash as a secondary raw material in building industry was also studied in terms of radiological aspects. Fly ash samples were taken at different stages along the emission control system of the thermal power plants. Activity concentrations of naturally occurring radionuclides were determined with Canberra Broad Energy Germanium (BEGe) detector BE3830-P and ORTEC Soloist PIPS type semiconductor detector. The particle size distribution and trace elements contents were determined in various ash fractions by the laser scattering particle size distribution analyzer and inductively coupled plasma (ICP-OES). From the obtained data, natural radionuclides tend to condense on fly ash with and the activity concentrations increase as the temperature drop in CPPs. Measured 210Pb and 210Po concentration varied between 186 ± 20-1153 ± 44 Bq kg-1, and 56 ± 5-1174 ± 45 Bq kg-1, respectively. The highest 210Pb and 210Po activity concentrations were determined in fly ash taken from the temporary storage point as 1153 ± 44 Bq kg-1 and 1174 ± 45 Bq kg-1, respectively. There were significant differences in the activity concentrations of some natural radionuclide and trace elements (Pb and Zn) contents in ash fractions among the sampling point inside both of the plants (ANOVA, p < 0.001). Coal and ash sample analysis showed an increase activity concentration and enrichment factors towards the electrostatic precipitators for both of the power plants. The enrichment factors for Zn follow a similar trend as Pb, increasing in value towards the end of the emission control system. The calculated activity indexes were above 1.0 value for both of the power plants, assuming the utilization of fly ash at 100%. It can be concluded that the reuse of fly ash as a secondary raw material may not be hazardous depending on the percentage of utilization of ash.


Acylhomoserine lactone synthase activity of the Vibrio fischeri AinS protein.
Acylhomoserine lactones, which serve as quorum-sensing signals in gram-negative bacteria, are produced by members of the LuxI family of synthases. LuxI is a Vibrio fischeri enzyme that catalyzes the synthesis of N-(3-oxohexanoyl)-L-homoserine lactone from an acyl-acyl carrier protein and S-adenosylmethionine. Another V. fischeri gene, ainS, directs the synthesis of N-octanoylhomoserine lactone. The AinS protein shows no significant sequence similarity with LuxI family members, but it does show sequence similarity with the Vibrio harveyi LuxM protein. The luxM gene is required for the synthesis of N-(3-hydroxybutyryl)-L-homoserine lactone. To gain insights about whether AinS and LuxM represent a second family of acylhomoserine lactone synthases, we have purified AinS as a maltose-binding protein (MBP) fusion protein. The purified MBP-AinS fusion protein catalyzed the synthesis of N-octanoylhomoserine lactone from S-adenosylmethionine and either octanoyl-acyl carrier protein or, to a lesser extent, octanoyl coenzyme A. With the exception that octanoyl coenzyme A served as an acyl substrate for the MBP-AinS fusion protein, the substrates for and reaction kinetics of the MBP-AinS fusion protein were similar to those of the several LuxI family members previously studied. We conclude that AinS is an acylhomoserine lactone synthase and that it represents a second family of such enzymes.


Effects of women with gestational diabetes mellitus related weight gain on pregnancy outcomes and its experiences in weight management programs: a mixed-methods systematic review.
Proper controlling gestational diabetes mellitus (GDM)-related gestational weight gain (GWG) during pregnancy can optimize pregnancy outcomes and improve postpartum glucose homeostasis. This study aimed to explore the existing intervention programs, the effects on pregnancy outcomes, and the experiences of weight management for GDM-related GWG in women with GDM. This mixed-methods systematic review was retrieved from nine databases. The retrieval time was from the database construction to September 20, 2023, and all studies were published in English and Chinese. The included records used quantitative, qualitative, or mixed methods and reported original studies of weight-related intervention regimens, effects on pregnancy outcomes, and women's experiences and perceptions. This review used a convergent segregated approach to synthesize and integrate research findings from Joanna Briggs Institute (JBI) mixed-methods systematic reviews. There were 16 articles that met the inclusion criteria, and the articles came from seven different countries and included 23,997 women with GDM. The meta-analysis pooled outcomes for the incidence of weight gain exceeding the Institute of Medicine (IOM) recommendations after GDM diagnosis to delivery was 0.31% (95% CI 0.21-0.42). The effectiveness of GDM-related weight interventions in reducing weight gain after GDM diagnosis was supported by quantitative evidence. The GDM-related GWG below the IOM recommendations is a protective factor (OR=0.68, 95%CI 0.48-0.97) for large for gestational Age (LGA), and above the IOM recommendations is a risk factor (OR=1.62, 95%CI 1.15-2.27) for LGA. In addition, no significant statistical significance was found in the pooled outcomes of small for gestational age (SGA). Avoiding excessive weight gain helps to optimize neonatal birth weight, pregnancy outcomes, and maternal blood glucose levels. According to qualitative survey results, some women with GDM experienced weight stigma, and a positive relationship between healthcare providers and GDM women helped in weight management. Following a diagnosis of GDM, weight management interventions positively affected GWG and pregnancy outcomes. In order to improve compliance and safety of weight management in women with GDM, criteria and interventions for weight gain associated with GDM need to be further explored and improved. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=404492, identifier CRD42023404492.


Deregulated E2F-1 blocks terminal differentiation and loss of leukemogenicity of M1 myeloblastic leukemia cells without abrogating induction of p15(INK4B) and p16(INK4A).
The transcription factor E2F-1 has been postulated to play a crucial role in the control of cell cycle progression because of its ability to be bound and regulated by the retinoblastoma gene product (pRb). Exogenous expression of E2F-1, under growth restrictive conditions, was shown to result in p53-dependent programmed cell death. The consequences of deregulated expression of E2F-1 on terminal differentiation of hematopoietic cells in the absence of E2F-1-mediated apoptosis, as well as mechanistic insights into how deregulated E2F-1 may affect terminal differentiation, have not been established. The autonomously proliferating M1 myeloblastic leukemia cell line, which is null for p53 expression and can be induced by interleukin-6 (IL-6) to undergo terminal macrophage differentiation with concomitant loss of leukemogenicity, provides a particularly attractive model system to address these issues. Deregulated and continued expression of E2F-1 blocked the IL-6-induced terminal differentiation program at an early blast stage, giving rise to immature cells, which continued to proliferate without undergoing apoptosis and retained their leukemogenic phenotype. Although E2F-1 blocked IL-6-mediated terminal differentiation and its associated growth arrest, it did not prevent the rapid induction of both p15(INK4B) and p16(INK4A), inhibition of cdk4 kinase activity, and subsequent hypophosphorylation of pRb. The results obtained imply that genetic alterations that both impair p53 function and deregulate E2F-1 expression may render hematopoietic cells refractory to the induction of differentiation and are, thereby, likely to play a major role in the progression of leukemias. (Blood. 2000;96:475-482)


[Significance of passive hemagglutination and its prospectives in lymphatic filariasis].
The authors analyze the data concerning 219 sera, that they have tested in passive hemagglutination, with as antigen a Dirofilaria immitis proteic extract, in French Polynesia. Besides its light sensitivity, this method does appear very interesting. It points out: --First, that there is a gaussian distribution of the results found at various dilutions, both by "filarian" and "non filarian" people. Therefore, this distribution is a feasible and practical parameter for evaluation of the Filariasis transmission in different populations. --On the other hand, that there is an inverse correlation between the presence of microfilaria in the blood and the level of immunological response for lymphatic Filariasis.


Regional density of glial cells in the rat corpus callosum.
Axons and glial cells are the main components of white matter. The corpus callosum (CC) is the largest white matter tract in mammals; in rodents, 99% of the cells correspond to glia after postnatal day 5 (P5). The area of the CC varies through life and regional differences related to the number of axons have been previously described. Whether glial cell density varies accordingly is unknown; thus the aim of this study was to estimate glial cell density for the genu, body and splenium -the three main regions of CC-, of P6 and P30 rats. Here we report that the density of CC glial cells reduced by ~10% from P6 to P30. Even so, the density of astrocytes showed a slight increase (+6%), probably due to differentiation of glioblasts. Interestingly, glial cell density decreased for the genu (-21%) and the body (-13%), while for the splenium a minor increase (+5%) was observed. The astrocyte/glia ratio increased (from P6 to P30) for the genu (+27%), body (+17%) and splenium (+4%). Together, our results showed regional differences in glial cell density of the CC. Whether this pattern is modified in some neuropathologies remains to be explored.


Assessment of synthetic red cell therapy for extremely preterm ovine fetuses maintained on an artificial placenta life-support platform.
Artificial placenta therapy (APT) is an experimental care strategy for extremely preterm infants born at 21-24 weeks' gestation. In our previous studies, blood taken from the maternal ewe was used as the basis of priming solutions for the artificial placenta circuit. However, the use of maternal blood as a priming solution is accompanied by several challenges. We explored the use of synthetic red cells (hemoglobin vesicles; HbV) as the basis of a priming solution for APT used to manage extremely early preterm ovine fetuses. Six ewes with singleton pregnancies at 95 d gestation (term = 150 d) were adapted to APT and maintained with constant monitoring of key vital parameters. The target maintenance period was 72 h in duration. A synthetic red cell solution consisting of HbV, sheep albumin and electrolytes was used as priming solutions for the APT circuit. Fetuses were evaluated on gross appearance, physiological parameters and bleeding after euthanasia. Two out of six APT fetuses were successfully maintained for the targeted 72 h experimental period with controllable anemia (>10 g/dl) and methemoglobinemia (<10%) using an infusion of blood transfusion and nitroglycerin delivered >1 h after APT commencement, a sufficient period of time to cross-match blood products and screen for viral agents of concern. Extremely preterm sheep fetuses were maintained for a period of up to 72 h using APT in combination with circuit priming using a synthetic red cell (HbV) preparation. Although significant further refinements are required, these findings demonstrated the potential clinical utility of synthetic blood products in the eventual clinical translation of artificial placenta technology to support extremely preterm infants.


Targeting CaN/NFAT in Alzheimer's brain degeneration.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive loss of cognitive functions. While the exact causes of this debilitating disorder remain elusive, numerous investigations have characterized its two core pathologies: the presence of β-amyloid plaques and tau tangles. Additionally, multiple studies of postmortem brain tissue, as well as results from AD preclinical models, have consistently demonstrated the presence of a sustained inflammatory response. As the persistent immune response is associated with neurodegeneration, it became clear that it may also exacerbate other AD pathologies, providing a link between the initial deposition of β-amyloid plaques and the later development of neurofibrillary tangles. Initially discovered in T cells, the nuclear factor of activated T-cells (NFAT) is one of the main transcription factors driving the expression of inflammatory genes and thus regulating immune responses. NFAT-dependent production of inflammatory mediators is controlled by Ca2+-dependent protein phosphatase calcineurin (CaN), which dephosphorylates NFAT and promotes its transcriptional activity. A substantial body of evidence has demonstrated that aberrant CaN/NFAT signaling is linked to several pathologies observed in AD, including neuronal apoptosis, synaptic deficits, and glia activation. In view of this, the role of NFAT isoforms in AD has been linked to disease progression at different stages, some of which are paralleled to diminished cognitive status. The use of classical inhibitors of CaN/NFAT signaling, such as tacrolimus or cyclosporine, or adeno-associated viruses to specifically inhibit astrocytic NFAT activation, has alleviated some symptoms of AD by diminishing β-amyloid neurotoxicity and neuroinflammation. In this article, we discuss the recent findings related to the contribution of CaN/NFAT signaling to the progression of AD and highlight the possible benefits of targeting this pathway in AD treatment.


[Body composition and obesity].
Obesity is a disease that is characterised by a pathological excess of adipose tissue. Normally, this excess is measured according to its repercussion on weight and on the index of body mass. The methods for measuring body composition, some of which are of recent introduction, are showing the consequences on health of excess fat, especially visceral fat. A review is offered of the epidemiological markers of obesity, the techniques for evaluating fatty mass, the influence of the distribution of the adipose tissue and the factors that condition visceral fat, as well as the influence of this tissue on the metabolic profile of the obese patient.


A modified silver technique (de Olmos stain) for assessment of neuronal and axonal degeneration.
Silver impregnation histological techniques yield excellent visualization of degenerating neurons and their processes in animal models of neurological diseases. These methods also provide a particularly valuable complement to current immunocytochemical techniques for recognition of axon injury in the setting of brain or spinal cord trauma, ischemia, or neurodegenerative diseases. Despite their utility, silver methods are not commonly used because of complex preparation requirements and inconsistent results obtained by inexperienced histologists. This chapter details a modification of the de Olmos amino-cupric-silver protocol, which has been adapted for efficient processing of large numbers of mouse or rat brains. One author (T.I.T.) has used this method for several years to identify degenerating neurons in adult and neonatal rodent brains. A detailed protocol is provided, with attention to the most critical variables in tissue fixation and solution preparation. Examples are shown of axon injury in the rat brain after focal ischemia.


Development and application of a sensitive method to determine concentrations of acrolein and other carbonyls in ambient air.
Acrolein, an unsaturated aldehyde, has been identified as one of the most important toxic air pollutants in recent assessments of ambient air quality. Current methods for determining acrolein concentrations, however, suffer from poor sensitivity, selectivity, and reproducibility. The collection and analysis of unsaturated carbonyls, and acrolein in particular, is complicated by unstable derivatives, coelution of similar compounds, and ozone interference. The primary objective of this research was to develop an analytical method to measure acrolein and other volatile carbonyls present in low part-per-trillion concentrations in ambient air samples obtained over short sampling periods. The method we devised uses a mist chamber in which carbonyls from air samples form water-soluble adducts with bisulfite in the chamber solution, effectively trapping the carbonyls in the solution. The mist chamber methodology proved effective, with collection efficiency for acrolein of at least 70% for each mist chamber at a flow rate of approximately 17 L/min. After the sample collection, the carbonyls are liberated from the bisulfite adducts through the addition of hydrogen peroxide, which converts the bisulfite to sulfate, reversing the bisulfite addition reaction. The free carbonyls are then derivatized by o-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA*), which stabilizes the analytes and makes them easier to detect by electron-capture negative ionization mass spectrometry (ECNI-MS). The derivatives are then extracted and analyzed by gas chromatography-mass spectrometry (GC-MS). The mist chamber method was applied in a field test to determine the extent of acrolein in ambient air near the Peace Bridge plaza in Buffalo, New York, an area of heavy traffic near a major border crossing between the United States and Canada. In addition, XAD-2 adsorbent cartridges coated with 2-(hydroxymethyl)piperidine (2-HMP) according to Occupational Safety and Health Administration (OSHA) Method 52 and passive samplers based on the use of dansylhydrazine (DNSH) were deployed at this location at the same time, which provided the opportunity to compare methods. The mist chamber results showed that the Peace Bridge traffic was clearly a source of acrolein, with an average concentration of 0.26 microg/m3 at a site 152.4 m downwind (northeast) of the plaza. The OSHA cartridges proved to be too insensitive to determine ambient acrolein concentrations. The DNSH passive samplers returned concentrations near the limit of detection; hence the values were a little higher and less consistent than those in the mist chamber results. The optimized mist chamber method was then applied to determine atmospheric acrolein concentrations at three sites in northern California: a site chosen to reflect the hemispheric background, a region dominated by biogenic sources, and an urban environment. The resulting average acrolein concentrations were 0.056, 0.089, and 0.290 microg/m3, respectively, and the limit of detection was 0.012 microg/m3 The consistency of the replicate samples obtained in the field was good, with the relative standard deviations (RSDs) ranging from 19% at the hemispheric background site to 3% at the urban site. The advantage of the current mist chamber method is that it can determine ambient acrolein concentrations over short time periods with enough sensitivity to be effective even in relatively "clean" environments. This allows for the determination of temporal patterns related to acrolein concentrations, such as diurnal cycles of reaction kinetics. The main disadvantages of the method are that it is laborious and time-consuming and requires specialized equipment that makes it difficult to utilize for routine monitoring of acrolein.


[Zinc-deficient states in man].
Pathology seen in zink deficiency in man is presented. In the antenatal period this deficiency leads to the delivery of immature fetuses and development of congenital malformations. In the postnatal period, zink deficiency can be produced by endogenic, exogenic, and iatrogenic causes. Zink deficient states are characterized by various clinical signs.


Estrogen inhibits vascular smooth muscle cell-dependent adventitial fibroblast migration in vitro.
Mounting experimental evidence suggests that estrogen treatment protects against neointima formation in response to vascular injury in vivo. Previous studies have suggested that this process includes the activation and migration of adventitial fibroblasts. The present in vitro study was designed to establish a mechanism whereby estrogen attenuates migration of adventitial fibroblasts. METHDS AND RESULTS: Primary cultures of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts were derived from female Sprague-Dawley rats. Reverse transcriptase-polymerase chain reaction and Western blotting were used to determine that expression of the estrogen receptor (ER) was restricted to early-passage VSMCs. Migration of transduced (retrovirally mediated) fibroblasts was determined by counting the number of blue lacZ-expressing cells attached to Boyden-type chambers preconditioned under defined experimental conditions. Compared with growth medium alone, chambers treated with medium conditioned by VSMCs demonstrated a 2-fold increase in fibroblast migration, suggesting that VSMCs release soluble factor(s) competent to bind the Transwell membrane and promote fibroblast migration. In contrast, treatment of VSMCs with 17beta-estradiol (10(-9) to 10(-7) mol/L) before preconditioning of the chamber induced a dose-dependent inhibition of fibroblast migration. Cotreatment of VSMCs with 17beta-estradiol and the ER antagonist ICI-182780 (10(-7) mol/L) blocked the inhibitory effect of estrogen on fibroblast migration. These observations suggest a novel mechanism of hormonal vasoprotection by which estrogen directly modulates VSMC expression of factor(s) controlling migration of adventitial fibroblasts via an ER-dependent mechanism.


Novel human and mouse homologs of Saccharomyces cerevisiae DNA polymerase eta.
The Saccharomyces cerevisiae RAD30 gene encodes a novel eukaryotic DNA polymerase, pol eta that is able to replicate across cis-syn cyclobutane pyrimidine dimers both accurately and efficiently. Very recently, a human homolog of RAD30 was identified, mutations in which result in the sunlight-sensitive, cancer-prone, Xeroderma pigmentosum variant group phenotype. We report here the cloning and localization of a second human homolog of RAD30. Interestingly, RAD30B is localized on chromosome 18q21.1 in a region that is often implicated in the etiology of many human cancers. The mouse homolog (Rad30b) is located on chromosome 18E2. The human RAD30B and mouse Rad30b mRNA transcripts, like many repair proteins, are highly expressed in the testis. In situ hybridization analysis indicates that expression of mouse Rad30b occurs predominantly in postmeiotic round spermatids. Database searches revealed genomic and EST sequences from other eukaryotes such as Aspergillus nidulans, Schizosaccharomyces pombe, Brugia malayi, Caenorhabditis elegans, Trypanosoma cruzi, Arabidopsis thaliana, and Drosophila melanogaster that also encode putative homologs of RAD30, thereby suggesting that Rad30-dependent translesion DNA synthesis is conserved within the eukaryotic kingdom.


The prevalence of mood and anxiety disorders in Australian women.
We aimed to report the prevalence, age-of-onset and comorbidity of mood and anxiety disorders in an age-stratified representative sample of Australian women aged 20 years and over. Mood and anxiety disorders were diagnosed utilising a clinical interview (SCID-I/NP). The lifetime and current prevalence of these disorders was determined from the study population (n = 1095) and standardized to 2006 census data for Australia. Approximately one in three women (34.8%) reported a lifetime history of any mood and/or anxiety disorder, with mood disorders (30.0%) being more prevalent than anxiety disorders (13.5%). Of these, major depression (23.4%), panic disorder (5.5%) and specific phobia (3.5%) were the most common. The lifetime prevalence of other disorders was low (< or =3%). A total of 14.4% of women were identified as having a current mood and/or anxiety disorder, with similar rates of mood (8.9%) and anxiety disorders (8.0%) observed. The median age-of-onset for mood disorders was 27.0 years and 18.5 years for anxiety disorders. This study reports the lifetime and current prevalence of mood and anxiety disorders in the Australian female population. The findings emphasize the extent of the burden of these disorders in the community.


[Enkephalins as regulators of physiological functions].
The problem of the regulation of the different physiological functions by enkephalines is discussed. A cite as an example the data about the regulatory action of the enkephalines on the secretory function of the stomach, pancreas and liver are discussed. The mechanisms of the enkephalines action on the secretory processes are discussed too.


Claudin-2 expression increases tumorigenicity of colon cancer cells: role of epidermal growth factor receptor activation.
Claudin-2 is a unique member of the claudin family of transmembrane proteins, as its expression is restricted to the leaky epithelium in vivo and correlates with epithelial leakiness in vitro. However, recent evidence suggests potential functions of claudin-2 that are relevant to neoplastic transformation and growth. In accordance, here we report, on the basis of analysis of mRNA and protein expression using a total of 309 patient samples that claudin-2 expression is significantly increased in colorectal cancer and correlates with cancer progression. We also report similar increases in claudin-2 expression in inflammatory bowel disease-associated colorectal cancer. Most importantly, we demonstrate that the increased claudin-2 expression in colorectal cancer is causally associated with tumor growth as forced claudin-2 expression in colon cancer cells that do not express claudin-2 resulted in significant increases in cell proliferation, anchorage-independent growth and tumor growth in vivo. We further show that the colonic microenvironment regulates claudin-2 expression in a manner dependent on signaling through the EGF receptor (EGFR), a key regulator of colon tumorigenesis. In addition, claudin-2 expression is specifically decreased in the colon of waved-2 mice, naturally deficient in EGFR activation. Furthermore, genetic silencing of claudin-2 expression in Caco-2, a colon cancer cell line, prevents the EGF-induced increase in cell proliferation. Taken together, these results uncover a novel role for claudin-2 in promoting colon cancer, potentially via EGFR transactivation.


Impaired Cerebellar Maturation, Growth Restriction, and Circulating Insulin-Like Growth Factor 1 in Preterm Rabbit Pups.
Cerebellar growth is impeded following very preterm birth in human infants and the observed reduction in cerebellar volume is associated with neurodevelopmental impairment. Decreased levels of circulating insulin-like growth factor 1 (IGF-1) are associated with decreased cerebellar volume. The relationship between preterm birth, circulating IGF-1, and key cell populations supporting cerebellar proliferation is unknown. The aim of this study was to evaluate the effect of preterm birth on postnatal growth, circulating IGF-1, and cerebellar maturation in a preterm rabbit pup model. Preterm rabbit pups (PT) were delivered by cesarean section at day 29 of gestation, cared for in closed incubators with humidified air, and gavage fed with formula. Control term pups (T) delivered by spontaneous vaginal delivery at day 32 of gestation were housed and fed by their lactating doe. In vivo perfusion-fixation for immunohistochemical evaluation of cerebellar proliferation, cell maturation, and apoptosis was performed at repeated time points in PT and T pups. Results show that the mean weight of the pups and circulating IGF-1 protein levels were lower in the PT group at all time points (p < 0.05) than in the T group. Postnatal weight development correlated with circulating IGF-1 (r2 = 0.89) independently of gestational age at birth and postnatal age. The proliferative (Ki-67-positive) portion of the external granular layer (EGL) was decreased in the PT group at postnatal day 2 (P2) compared to in the T group (p = 0.01). Purkinje cells exhibited decreased calbindin staining at P0 (p = 0.003), P2 (p = 0.004), and P5 (p = 0.04) in the PT group compared to in the T group. Staining for sonic hedgehog was positive in neuronal EGL progenitors and Purkinje cells at early time points but was restricted to a well-defined Purkinje cell monolayer at later time points. Preterm birth in rabbit pups is associated with lower circulating levels of IGF-1, decreased postnatal growth, and decreased cerebellar EGL proliferation and Purkinje cell maturation. The preterm rabbit pup model exhibits important characteristics of human preterm birth, and may thus be suitable for the evaluation of interventions aiming to modify growth and cerebellar development in the preterm population.


Investigative drugs for the treatment of cutaneous T-cell lymphomas (CTCL): an update.
Introduction: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Mycosis fungoides and Sézary syndrome are the most common CTCL. Early stage disease follows a protracted course, carries a 5-year disease specific survival of 97% and can be treated with skin-directed therapies. Widespread, advanced disease has a 5-year OS of less than 25% and necessitates systemic treatment. Allogeneic stem cell transplantation is a potentially curative treatment option for advanced CTCL, however, transplant-related morbidity and mortality must be considered and a risk-benefit assessment performed on individual basis. Areas covered: Herein, we provide a review of investigative drugs in early-stage trials for the treatment of cutaneous CTCL, including topically applied immunomodulators such as replicating herpes virus or toll-like receptor 7/8 agonist resiquimod and systemic therapies with monoclonal antibodies, such as anti-CD47, recombinant cytotoxic interleukin 2 fusion protein anti-KIR3DL2 antibody and anti-miR-155 antibody. Expert Opinion: Among the reviewed drugs, resiquimod shows promising clinical efficacy with good tolerability in early CTCL. In refractory or relapsed disease, intratumoral anti-CD47-, anti-CCR4- and anti-KIR3DL2-antibodies show high response rates, however, latter two also show considerable toxicity. Larger trials are needed to better evaluate the discussed therapies.


Non-invasive respiratory support for the management of transient tachypnea of the newborn.
Transient tachypnea of the newborn (TTN) is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of life in term and late preterm newborns. Supportive management might be sufficient. Non-invasive (i.e. without endotracheal intubation) respiratory support may, however, be administered to reduce respiratory distress during TTN. In addition, non-invasive respiratory support might improve clearance of lung liquid thus reducing the effort required to breathe, improving respiratory distress and potentially reducing the duration of tachypnea. To assess benefits and harms of non-invasive respiratory support for the management of transient tachypnea of the newborn. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 2), MEDLINE (1996 to 19 February 2019), Embase (1980 to 19 February 2019) and CINAHL (1982 to 19 February 2019). We applied no language restrictions. We searched clinical trial registries for ongoing studies. Randomized controlled trials, quasi-randomized controlled trials and cluster trials on non-invasive respiratory support provided to infants born at 34 weeks' gestational age or more and less than three days of age with transient tachypnea of the newborn. For each of the included trials, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, duration of oxygen therapy, need for continuous positive airway pressure [CPAP] and need for mechanical ventilation, duration of mechanical ventilation, etc.) and assessed the risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). The primary outcomes considered in this review were need for mechanical ventilation and pneumothorax. We used the GRADE approach to assess the certainty of evidence. We included three trials (150 infants) comparing either CPAP to free-flow oxygen, nasal intermittent mandatory ventilation to nasal CPAP, or nasal high-frequency percussive ventilation versus nasal CPAP. Due to these different comparisons and to high clinical heterogeneity in the baseline clinical characteristics, we did not pool the three studies. The use of CPAP versus free oxygen did not improve the primary outcomes of this review: need for mechanical ventilation (risk ratio [RR] 0.30, 95% confidence interval [CI] 0.01 to 6.99; 1 study, 64 participants); and pneumothorax (not estimable, no cases occurred). Among secondary outcomes, CPAP reduced the duration of tachypnea as compared to free oxygen (mean difference [MD] -21.10 hours, 95% CI -22.92 to -19.28; 1 study, 64 participants). Nasal intermittent ventilation did not reduce the need for mechanical ventilation as compared with CPAP (RR 4.00, 95% CI 0.49 to 32.72; 1 study, 40 participants) or the incidence of pneumothorax (RR 1.00, 95% CI 0.07 to 14.90; 1 study, 40 participants); duration of tachypnea did not differ (MD 4.30, 95% CI -19.14 to 27.74; 1 study, 40 participants). In the study comparing nasal high-frequency ventilation to CPAP, no cases of mechanical ventilation of pneumothorax occurred (not estimable; 1 study, 46 participants); duration of tachypnea was reduced in the nasal high-frequency ventilation group (MD -4.53, 95% CI -5.64 to -3.42; 1 study, 46 participants). The quality of the evidence was very low due to the imprecision of the estimates and unclear risk of bias for detection bias and high risk of bias for reporting bias. Tests for heterogeneity were not applicable for any of the analyses as no studies were pooled. Two trials are ongoing. There is insufficient evidence to establish the benefit and harms of non-invasive respiratory support in the management of transient tachypnea of the newborn. Though two of the included trials showed a shorter duration of tachypnea, clinically relevant outcomes did not differ amongst the groups. Given the limited and low quality of the evidence available, it was impossible to determine whether non-invasive respiratory support was safe or effective for the treatment of transient tachypnea of the newborn.


Pityriasis lichenoides in children: clinicopathologic review of 22 patients.
Pityriasis lichenoides (PL) is a cutaneous disease of unknown origin, with an autoinvolutive course, that can occur in pediatric patients. Traditionally, acute and chronic variants have been described, but other special forms of presentation have been reported. We reviewed the clinical records and histopathologic specimens of all pediatric patients diagnosed with PL in our hospital from 1980 to 1995 to assess the clinicopathologic features of this disorder in our environment. Twenty-two of the 118 cases reviewed were pediatric patients less than 15 years old (12 males and 10 females, 18.6% of all patients). Their ages ranged from 3 to 15 years, with a mean of 9.3 years. Most of the patients (72%) had the chronic variant of the disease, while the remainder had an acute course. One patient suffered from acute ulceronecrotic PL. Systemic treatments prescribed were erythromycin in eight patients, PUVA in five patients, and methotrexate in one patient. Three patients had a prolonged course with more than two episodes. Acute and chronic PL are polar extremes, but individual cases cannot be classified only on the basis of histopathologic data, since coexistence of lesions in different stages of evolution can lead to sampling bias. Acute ulceronecrotic forms and the presence of a variable degree of cellular atypia in the infiltrate are liable to cause differential diagnostic problems with lymphomatoid papulosis (LP), which cannot be completely resolved on the basis of T-cell receptor clonal rearrangement detection.


The Political Psychology of COVID-19.
The COVID-19 pandemic has given rise to unprecedented and extraordinary conditions. It represents a profound threat to health and political and economic stability globally. It is the pressing issue of the current historical moment and is likely to have far-reaching social and political implications over the next decade. Political psychology can inform our preparedness for the next phase of the pandemic as well as our planning for a post COVID-19 world. We hope that this special issue will play its part in helping us to think how we manage and live with COVID-19 over the coming decade. In this editorial, we review the key themes arising from the contributions to our special issue and, alongside existing knowledge highlight the relevance of political psychology to finding solutions during this time of crisis. The contributions to this special issue and the pandemic raise many classic topics of central interest to political psychology: leadership, solidarity and division, nationalism, equality, racism, and international and intergroup relations. In our editorial, we offer an analysis that highlights three key themes. First, the importance of sociopolitical factors in shaping behavior during this pandemic. Second, the relevance of political leadership and rhetoric to collective efforts to tackle SARS-COV-2. And third, how sociopolitical cohesion and division has become increasingly relevant during this time of threat and crisis.


Incidental colonic focal lesions detected by FDG PET/CT.
The aim of this study was to assess the performance of FDG PET/CT for the detection of colonic lesions, especially advanced neoplasms (villous or >10-mm adenomas, carcinomas). Because of 18F FDG accumulation in adenomatous polyps, PET using FDG can detect early premalignant colorectal lesions. FDG PET/CT studies performed for a 1-year period in 1,716 consecutive patients with various malignant diseases, except colorectal cancer, were retrospectively reviewed. PET images obtained 1 hr after FDG injection and non-contrast CT images used for attenuation correction were fused for analysis. Of 45 patients showing intense focal colonic FDG uptake, 20 patients (with 21 foci) underwent a colonoscopic investigation, and, when necessary, polyp resection. The intensity of FDG uptake was quantified using the standardized uptake value (SUV(max)). The FDG colonic foci were associated with 18 colonoscopic abnormalities in 15 patients, with no colonic abnormality detected in five patients (false-positive [FP] results). Histopathologic findings revealed advanced neoplasms in 13 patients (13 villous adenomas and three carcinomas) and two cases of hyperplastic polyps. A difference in the mean SUV(max) was found between FP and true-positive colonic FDG foci but was not statistically significant (p = 0.14). Presence of a focal colonic FDG uptake incidental finding on a PET/CT scan justifies a colonoscopy to detect (pre-)malignant lesions. The fusion of PET and CT images allows an accurate localization of the lesions. PET/CT is a useful tool to differentiate pathologic from physiologic FDG uptake.