Autosomal dominant distal spinal muscular atrophy type V (dSMA-V) and Charcot-Marie-Tooth disease type 2D (CMT2D) segregate within a single large kindred and map to a refined region on chromosome 7p15.
Two separate disorders, autosomal dominant distal spinal muscular atrophy type V (dSMA-V) characterized by marked bilateral weakness in the hands and atrophy of thenar eminence and the first interosseous muscle, and Charcot-Marie-Tooth disease type 2D (CMT2D) characterized by sensory deficits in addition to the upper limb weakness and wasting, have been independently linked to chromosome 7p. We identified a multigenerational Mongolian kindred with 17 members affected with either dSMA-V or CMT2D and mapped both syndromes to the same region on chromosome 7p15. A maximum two-point lod score of 4.74 at recombination fraction zero was obtained with marker D7S474. Tight linkage without recombination was also detected with markers D7S526 and D7S632. A multipoint lod score of 6.07 suggested that the gene is located between markers D7S526 and D7S474. A single conserved haplotype was associated with dSMA-V and CMT2D. Based on informative recombination events, the disease locus was placed between markers D7S516 and D7S1514 within the 7p15 band. Data obtained from this study suggest that a single gene is responsible for both syndromes, dSMA-V and CMT2D, and extend our knowledge of the candidate region.


Structural basis of γ chain family receptor sharing at the membrane level.
Common γ chain (γc) cytokine receptors, including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21 receptors, are activated upon engagement with a common γc receptor (CD132) by concomitant binding of their ectodomains to an interleukin. In this work, we find that direct interactions between the transmembrane domains (TMDs) of both the γc and the interleukin receptors (ILRs) are also required for receptor activation. Moreover, the same γc TMD can specifically recognize multiple ILR TMDs of diverse sequences within the family. Heterodimer structures of γc TMD bound to IL-7 and IL-9 receptor TMDs-determined in a lipid bilayer-like environment by nuclear magnetic resonance spectroscopy-reveal a conserved knob-into-hole mechanism of recognition that mediates receptor sharing within the membrane. Thus, signaling in the γc receptor family requires specific heterotypic interactions of the TMDs.


t(6;12)(q23;q13) and t(10;16)(q22;p11) in a phyllodes tumor of breast.
Cytogenetic analysis of short-term cultures from a phyllodes tumor showed clonal chromosome changes including t(6;12)(q23;q13) and t(10;16)(q22;p11). This is the first reported karyotype in this tumor type. We discuss the breakpoints of these translocations in relation to the involvement of possible candidate genes.


Effective surveillance systems for vector-borne diseases in urban settings and translation of the data into action: a scoping review.
Vector-borne diseases (VBDs) continue to represent a global threat, with "old" diseases like malaria, and "emergent" or "re-emergent" ones like Zika, because of an increase in international trade, demographic growth, and rapid urbanization. In this era of globalization, surveillance is a key element in controlling VBDs in urban settings, but surveillance alone cannot solve the problem. A review of experiences is of interest to examine other solution elements. The objectives were to assess the different means of VBD surveillance in urban environments, to evaluate their potential for supporting public health actions, and to describe the tools used for public health actions, the constraints they face, and the research and health action gaps to be filled. For this scoping review we searched peer-reviewed articles and grey literature published between 2000 and 2016. Various tools were used for data coding and extraction. A quality assessment was done for each study reviewed, and descriptive characteristics and data on implementation process and transferability were analyzed in all studies. After screening 414 full-text articles, we retained a total of 79 articles for review. The main targets of the articles were arboviral diseases (65.8%) and malaria (16.5%). The positive aspects of many studies fit within the framework of integrated vector management. Public awareness is considered a key to successful vector control programs. Advocacy and legislation can reinforce both empowerment and capacity building. These can be achieved by collaboration within the health sector and with other sectors. Research is needed to develop well designed studies and new tools for surveillance and control. The need for surveillance systems in urban settings in both developing and developed countries was highlighted. Countries face the same challenges relating to human, financial, and structural resources. These findings also constitute a wake-up call for governments, academia, funders, and World Health Organization to strengthen control programs and enhance VBD research in urban environments.


Recovery of platinum group metal resources from high-level radioactive liquid wastes by non-contact photoreduction.
Recovery of platinum group metals (PGMs) including palladium (Pd), rhodium (Rh), and ruthenium (Ru) from high-level radioactive liquid waste (HLLW) possesses enormous environmental and economic benefits. A non-contact photoreduction method was herein developed to selectively recover each PGM from HLLW. Soluble Pd(II), Rh(III), and Ru(III) ions were reduced to insoluble zero-valent metals and separated from simulated HLLW containing neodymium (Nd) as a representative for lanthanides, another main component in HLLW. Detailed investigation on the photoreduction of different PGMs revealed that Pd(II) could be reduced under 254- or 300-nm UV exposure using either ethanol or isopropanol as reductants. Only 300-nm UV light enabled the reduction of Rh(III) in the presence of ethanol or isopropanol. Ru(III) was the most difficult to reduce, which was only realized by 300-nm UV illumination in isopropanol solution. The effects of pH was also studied, suggesting that lower pH favored the separation of Rh(III) but hindered the reduction of Pd(II) and Ru(III). A delicate three-step process was accordingly designed to achieve the selective recovery of each PGM from simulated HLLW. Pd(II) was reduced by 254-nm UV light with the help of ethanol in the first step. Then Rh(III) was reduced by 300-UV light in the second step after the pH was adjusted to 0.5 to suppress the Ru(III) reduction. In the third step, Ru(III) was reduced by 300-nm UV light after isopropanol was added and the pH was adjusted to 3.2. The separation ratios of Pd, Rh, and Ru exceeded 99.8%, 99.9%, and 90.0%, respectively. Meanwhile, all Nd(III) still remained in the simulated HLLW. The separation coefficients between Pd/Rh and Rh/Ru exceeded 56,000 and 75,000, respectively. This work may provide an alternative method to recover PGMs from HLLW, which minimize the secondary radioactive wastes compared with other approaches.


Comparison of Tunable Diode Laser Absorption Spectroscopy and Isothermal Micro-calorimetry for Non-invasive Detection of Microbial Growth in Media Fills.
Two methods were investigated for non-invasive microbial growth-detection in intact glass vials as possible techniques for automated inspection of media-filled units. Tunable diode laser absorption spectroscopy (TDLAS) was used to determine microbially induced changes in O2 and CO2 concentrations within the vial headspaces. Isothermal microcalorimetry (IMC) allowed the detection of metabolic heat production. Bacillus subtilis and Streptococcus salivarius were chosen as test organisms. Parameters as robustness, sensitivity, comparability and time to detection (TtD) were evaluated to assess method adequacy. Both methods robustly detected growth of the tested microorganisms within less than 76 hours using an initial inoculum of <10CFU. TDLA turned out to be less sensitive than TDLA and IMC, as some false negative results were observed. Compared to the visual media-fill examination of spiked samples, the investigated techniques were slightly slower regarding TtD. Although IMC showed shorter TtD than TDLAS the latter is proposed for automating the media-fill inspection, as larger throughput can be achieved. For routine use either TDLA or a combination of TDLA and TDLA should be considered. IMC may be helpful for replacing the sterility assessment of commercial drug products before release.


Nutritionists as policy advocates: the case of obesity prevention in Quebec, Canada.
A core function of the public health nutrition workforce is advocacy. Little is known of the nutritionists' role in policymaking from a policy process theory perspective. The current study analyses the nutritionists' role in advocating for a six-year governmental plan on obesity prevention in Quebec, Canada. We conducted qualitative research using Quebec's obesity policy as a case study to understand the role of nutritionists in advocating for obesity prevention policies. A conceptual framework combining the Advocacy Coalition Framework with a political analysis model based on the Theory of the Strategic Actor was developed to analyse the beliefs, interests and strategies of policy actors including nutritionists. Data sources comprised semi-structured open-ended interviews with key policy actors (n 25), including eight nutritionists (32 %) and policy-related documents (n 267). Data analysis involved thematic coding and analysis using NVivo 11 Pro. Quebec, Canada. Key policy actors including nutritionists. Nutritionists formed the core of the dominant public health coalition. They advocated for an inter-sectoral governmental plan to prevent obesity through enabling environments. Their advocacy, developed through an iterative process, comprised creating a think tank and reinforcing partnerships with key policy actors, conducting research and developing evidence, communicating policy positions and advocacy materials, participating in deliberative forums and negotiating an agreement with other coalitions in the policy subsystem. Nutritionists' advocacy influenced agenda setting and policy formulation. This research may contribute to empowering the public health nutrition workforce and strengthening its advocacy practices. It informs practitioners and researchers concerned with obesity policy and workforce development.


[Dermatophytoses found at the Pasteur Institute of Tunis. Apropos of 697 cases].
A study about 697 patients with fungous injuries of scalp and hairless skin shows that 50% of scalp lesions and 16% of hairless skin lesions are dermatophyties. The incidence of dermatophytes is stable since the last study of Juminer in Tunis (1964); Trichophyton violaceum is the most identified fungous; however, we attend the push of zoo-anthropophil dermatophytes, so that Microsporum canis.


Langerhans cells are not required for efficient skin graft rejection.
The mechanism of skin allograft rejection has been thought to require presentation of graft antigen by resident epidermal Langerhans cells (LCs). We have previously engineered mice that have a selective and constitutive absence of epidermal LCs. By using donor skin from these LC-deficient mice, we show that LCs are not required for rejection of major (FVB --> B6) or minor (H-Y, male --> female on B6 background) antigen-mismatched skin grafts. On the FVB background, where H-Y mismatched grafts are normally maintained indefinitely, grafts lacking LCs are efficiently rejected. Thus, LCs in the donor graft are required for long-term skin engraftment, which supports a regulatory role for LCs in skin graft acceptance.


Outcomes based on histopathologic response to preoperative chemotherapy in children with bilateral Wilms tumor: A prospective study (COG AREN0534).
An objective of the Children's Oncology Group AREN0534 Study was to improve the survival of patients with bilateral Wilms tumors (BWT) by using preoperative chemotherapy of limited duration and tailoring postoperative therapy based on histopathologic response. The authors report outcomes based on postoperative histopathologic responses. Patients with BWT received treatment with vincristine, dactinomycin, and doxorubicin for 6 or 12 weeks followed by surgery. Postoperative therapy was prescribed based on the highest risk tumor according to the International Society of Pediatric Oncology classification and the Children's Oncology Group staging system. Analyses were performed on data from 180 evaluable children. The 4-year event-free survival (EFS) and overall survival (OS) rates were 81% (95% CI, 74%-87%) and 95% (95% CI, 91%-99%), respectively. Seven patients who had completely necrotic tumors had a 4-year EFS rate of 100%. Of 118 patients who had tumors with intermediate-risk histopathology, the 4-year EFS and OS rates were 82% (95% CI, 74%-90%) and 97% (95% CI, 94%-100%), respectively. Fourteen patients who had blastemal-type tumors had 4-year EFS and OS rates of 79% (95% CI, 56%-100%) and 93% (95% CI, 79%-100%), respectively. Eighteen patients who had diffuse anaplasia had 4-year EFS and OS rates of 61% (95% CI, 35%-88%) and 72% (95% CI, 47%-97%), respectively; and the 4-year EFS and OS rates of 7 patients who had focal anaplasia were 71% (95% CI, 38%-100%) and 100%, respectively. There was no difference in the outcomes of patients who had different histopathologic subtypes within the intermediate-risk group (P = .54). A risk-adapted treatment approach for BWT results in excellent outcomes. This approach was not successful in improving the outcome of patients who had diffuse anaplasia.


Engineering of chicken avidin: a progressive series of reduced charge mutants.
Avidin, a positively charged egg-white glycoprotein, is a widely used tool in biotechnological applications because of its ability to bind biotin strongly. The high pI of avidin (approximately 10.5), however, is a hindrance in certain applications due to non-specific (charge-related) binding. Here we report a construction of a series of avidin charge mutants with pIs ranging from 9.4 to 4.7. Rational design of the avidin mutants was based on known crystallographic data together with comparative sequence alignment of avidin, streptavidin and a set of avidin-related genes which occur in the chicken genome. All charge mutants retained the ability to bind biotin tightly according to optical biosensor interaction analysis. In most cases, their thermal stability characteristics were indistinguishable from those of the wild-type avidin. Our results demonstrate that the charge properties of avidin can be modified without disturbing the crucial biotin-binding activity.


4D radial coronary artery imaging within a single breath-hold: cine angiography with phase-sensitive fat suppression (CAPS).
Coronary artery data acquisition with steady-state free precession (SSFP) is typically performed in a single frame in mid-diastole with a spectrally selective pulse to suppress epicardial fat signal. Data are acquired while the signal approaches steady state, which may lead to artifacts from the SSFP transient response. To avoid sensitivity to cardiac motion, an accurate trigger delay and data acquisition window must be determined. Cine data acquisition is an alternative approach for resolving these limitations. However, it is challenging to use conventional fat saturation with cine imaging because it interrupts the steady-state condition. The purpose of this study was to develop a 4D coronary artery imaging technique, termed "cine angiography with phase-sensitive fat suppression" (CAPS), that would result in high temporal and spatial resolution simultaneously. A 3D radial stacked k-space was acquired over the entire cardiac cycle and then interleaved with a sliding window. Sensitivity-encoded (SENSE) reconstruction with rescaling was developed to reduce streak artifact and noise. Phase-sensitive SSFP was employed for fat suppression using phase detection. Experimental studies were performed on volunteers. The proposed technique provides high-resolution coronary artery imaging for all cardiac phases, and allows multiple images at mid-diastole to be averaged, thus enhancing the signal-to-noise ratio (SNR) and vessel delineation.


Isolation and characterization of histones from Anopheles albimanus Weidemann.
1. Histones from Anopheles albimanus adults were prepared by a combination of techniques including chromatin isolation and selective extractions. 2. The anopheline histones were identified on acid urea gels by comparing their electrophoretic profile with that of calf thymus histones and histones isolated from other tissue. 3. Excellent separation of histones was obtained after the extractions by a single electrophoretic run. 4. In addition to the five major classes of histones found in eukaryotes, a sixth class was detected and tentatively identified as histone H5. 5. This is the first report of histone H5 and its function in insects.


[Spontaneous myospherulosis developing at contact with a mature cystic dysembryoma of the ovary. Pathogenetic discussion apropos of a case diagnosed by laparoscopic biopsy].
The author has reported a case of spontaneous myospherulosis which developed adjacent to a benign cystic ovarian teratoma which was discovered by routine ultrasound examination in a young patient admitted for spontaneous abortion. This ovarian cyst had not been aspirated before. This report demonstrates that myospherulosis can be induced spontaneously by necrosis of fatty tissues. Up to now, this lesion was considered iatrogenic. In this case, it resulted from a physical process similar to the emulsion phenomenon between intra-tissular free fatty materials and plasma. This process gives rise to sequestration of blood cells, in particular erythrocytes by free fatty materials with the formation of "bags of marbles". These saccular structures thus produce inflammatory changes with foreign body granuloma and pseudo-cystization.


Recovery and assessment of leukocytes from LR Express filters.
Leukocytes, or white blood cells, are used for a variety of investigational purposes and they offer advantages over laboratory-adapted cell lines. Leukocytes that are typically discarded by blood banks during the collection of red blood cells, platelets, and plasma can often be obtained for research use. However, the available leukocytes are frequently contained within a blood filtration device, such as the Terumo LR Express (TLRE) filter. In this study, procedures were evaluated for the ability to elute viable leukocytes from TLRE filters. The recovered leukocytes were assessed for composition, growth, and functionality. The large majority (>70%) of leukocytes were eluted with a single reverse-elution procedure and the recovered cells contained representative populations of the major leukocyte subsets. Purified T cells exhibited diverse T cell receptor repertoires, characteristic growth upon mitogen stimulation, and CD4+ T cells were able to support HIV-1 propagation. Purified monocytes were able to be differentiated into phenotypically characteristic populations of macrophages and dendritic cells. Overall, TLRE filters offer an attractive source of primary human cells for research and possibly clinical purposes.


Self-control and frequency of model presentation: effects on learning a ballet passé relevé.
The purpose of this experiment was to examine the combined effects of self-control and frequency of model presentation on learning a complex motor skill, i.e., ballet passé relevé. Before practice started self-control participants were asked to choose two viewings or six viewings (before practice and then every five trials) and the externally controlled groups were yoked to their self-control counterparts. All participants completed 15 acquisition trials followed by 5 trials for the immediate and 5 trials for the delayed retention tests 48 hours later. Dependent variables included cognitive representation scores, physical reproduction rankings, and balance time. Statistical analyses indicated that under limited physical practice conditions self-control and higher frequency of model presentation facilitated the development of cognitive representation and did not produce further benefits in movement reproductions and balance time. The results were discussed with respect to the social cognitive theory.


Interdisciplinary health education: a case study of fact and fancy.
Meeting the health needs of patients and providing comphrehensive health care services require the integration and coordination of several professional health services. Traditional methods for training students in the health professions independently are being challenged by the need for future practitioners to understand and to utilize effectively the skills offered by the other disciplines. However, the movement of educational institutions toward interdisciplinary training programs entails the careful assessment of program design, content, and basic philosophy. Two and one-half years of experience with such a program at one academic health center are reviewed.


New trends and clinical patterns of human trichinellosis in Russia at the beginning of the XXI century.
Official national statistics show a gradual decline in the incidence of trichinellosis in Russia from 971 cases in 1996 to 527 cases in 2002. Of the total 864 cases involved in 47 trichinellosis outbreaks during 1998--2002, only 35.8% were due to infected pork compared to 80% in 1995--1996. Other important sources were wild animals, such as bear (Ursus arctos) (39.5%), badger (Meles meles) (10.6%), and dog meat (11.9%). Children composed 15.9% of all cases. Overall, 81.0% of pork-cases occurred in the European part of the country, and 89.4% of bear-meat cases were from the Asian region where most of the badger and dog-meat cases also originated. The percent of clinically severe cases of disease derived from pork and from bear meat was 7.7% and 7.9%, respectively; the frequency of moderate cases from pork was significantly higher than from bear meat. Clinically severe cases from badger and dog meat were 1.1% and 1.9%, respectively, where the number of clinically moderate cases from badger meat was significantly larger than that from dog meat. A disturbing trend is the 52.3% of trichinellosis cases during 1998--2002 in Russia that were derived from wild animal meat, especially the clinically severe cases occurring among the aboriginal Siberian population. The contributing factors to the slow decline in trichinellosis incidence in Russia and to the increase in percentage of cases originating from wild animal meat are the distribution and consumption of veterinary-uncontrolled pork, poaching and distribution of wild animal meat, and the neglect of medical and civil regulations. These trends should be seriously evaluated by the institutions of health, education, and by the veterinary service.


[Evaluating a child after a febrile seizure: Insights on three important issues].
Febrile seizures (FS) are the most common seizures seen in the paediatric population in the out-of-hospital and emergency department settings, and they account for the majority of seizures seen in children younger than 5 years old. An FS is a seizure accompanied by fever, without central nervous system infection, occurring in children between 6 months and 5 years old. Five criteria have been used and taught to classify any FS as simple or complex FS. These factors do not bear the same significance for clinical practice, in particular, the decision to perform a lumbar puncture for cerebrospinal fluid analysis to rule out an intracranial infection. Moreover, epidemiological studies have illustrated that some factors are predictive of febrile seizure recurrence while others are predictive of epilepsy occurrence. On this basis, a workshop was organized to provide an answer to three clinical practice questions: when should a lumbar puncture be performed in a child who has experienced a seizure during a fever episode, is the prescription of a rescue drug required with a risk of a prolonged febrile seizure recurrence, when should a neurological consultation be requested (risk of later epilepsy)? Based on a review of the literature and on a 1-day workshop, we report here the conclusion of the working group. A lumbar puncture is required in any child with meningitis symptoms or septic signs or behaviour disturbance. A lumbar puncture should be discussed based on the clinical symptoms and their progression over time when a child has experienced a focal FS or repetitive FSs without signs of meningitis or sepsis or behaviour disturbance. The lumbar puncture is not necessary in case of simple FS without signs of meningitis, including in infants between 6 and 12 months old. An early clinical evaluation (at least 4 h after the first clinical assessment) could be helpful, in particular in infants younger than 12 months of age. A rescue drug might be prescribed when there is a high risk of prolonged FS (i.e., risk higher than 20%): age at FS<12months OR a history of a previous febrile status epilepticus OR if the first FS was a focal seizure OR abnormal development/neurological exam/MRI OR a family history of nonfebrile seizure. A neurological consultation should be requested for any child who has experienced a prolonged FS before the age of 1 year, for children who have experienced prolonged and focal FS or repetitive (within 24h) focal FS, for children who have experienced multiple complex (focal or prolonged or repetitive) FS, for children with an abnormal neurological exam or abnormal development experiencing a FS. Although childhood febrile seizures in most cases are benign, witnessing such seizures is always a terrifying experience for the child's parents. Most parents feel that their child is dying or could have severe brain injury related to the episode. Therefore, the group also suggests a post-FS visit with the primary care physician.


The effect of smoking on inflammatory cell infiltrate subtypes in gingival tissue of patients with chronic periodontitis.
Examinations on blood samples and gingival crevicular fluid of subjects with chronic periodontitis showed that smoking increased production of cytokines. To evaluate the expression of immune markers on mononuclear inflammatory cell infiltrate at periodontitis and healthy tissue among smoking and non-smoking subjects. This case-control study was performed on 41 patients who referred to a clinic of periodontology at a Mashhad dental school in Iran in 2016. The participants were all of Iranian Khorasanian ethnicity with age range of 35-65 years. Gingival biopsies were obtained during routine periodontal flap procedure. Immunohistochemistry using markers of CD20, CD3, CD68, and CD45RO was carried out. Data was analyzed by SPSS version 15, using one-way ANOVA and Tukey HSD test. Nonsmoker subjects showed significantly greater numbers of CD20+, CD68+, CD3+ cells compared to smoker subjects, both at healthy and periodontitis tissue biopsies (p<0.00), whereas there was no significant difference in terms of CD45RO (p=0.120). Cigarette smoking, results in infiltrative mononuclear chronic inflammatory cells reduction in connective periodontium.


Technique for All-Inside Anterior Cruciate Ligament Reconstruction Using Quadrupled Semitendinosus and Gracilis Autograft.
Anterior cruciate ligament (ACL) injuries are common to athletes and non-athletes alike. Whereas the literature has historically supported bone-patellar tendon-bone as the gold standard for active patients who elect to undergo ACL reconstruction, other studies have suggested that soft-tissue grafts do not increase the risk of rerupture. Because graft diameter has a direct effect on revision rates, we share a technique for all-inside ACL reconstruction using quadrupled semitendinosus and gracilis autograft that allows for a predictable, robust graft. Reproducible steps of graft harvesting, tunnel preparation, graft passage, and fixation are shared to achieve a robust anatomic reconstruction.


Correction: Use of the 'Accountability for Reasonableness' Approach to Improve Fairness in Accessing Dialysis in a Middle-Income Country.
[This corrects the article DOI: 10.1371/journal.pone.0164201.].


Transposition of a plasmid deoxyribonucleic acid sequence that mediates ampicillin resistance: identity of laboratory-constructed plasmids and clinical isolates.
The structural gene for ampicillin resistance resides upon a 3.2 X 10(6)-dalton sequence of deoxyribonucleic acid, TnA that can be transposed from replicon to replicon in laboratory experiments. TnA was transposed from a large conjugative plasmid to a small nonconjugative plasmid, RSF1010. Several RSF1010::TnA plasmids isolated in these laboratory experiments have been shown to be identical to plasmids found in clinical isolates. These data provide direct support to the theory that transposition of drug resistance genes play a key role in the evolution of R plasmids.


REM sleep and bradyarrhythmia episodes in rats.
The relationship between rapid eye movement (REM) phasic events and bradyarrhythmia was investigated in five male Wistar rats. ECGs, EEGs (frontal cortex and dorsal hippocampus), and electrooculograms were monitored continuously for 6 days. Sleep states were classified as alertness, slow-wave sleep, or paradoxical sleep, and the frequency of the REM burst was measured to evaluate the REM density. Bradyarrhythmias, such as SA block or AV block, were observed in each rat and were divided into two groups: group A, bradyarrhythmias with a duration greater than 5 sec; and group B, duration less than 5 sec. For a period of 33 days, the five rats showed alertness, slow-wave sleep, and paradoxical sleep 6,481, 6,483, and 1,523 times; bradyarrhythmia incidents in each sleep stage were 0.35%, 0.03%, and 22.4%, respectively. The incidence of bradyarrhythmia episodes increased with REM density, and 78.5% of the episodes appeared related to the REM bursts. The latency between the REM bursts and bradyarrhythmia was as follows: type A bradyarrhythmias, 2.17 +/- 0.41 sec; type B, 3.78 +/- 0.63 sec. These results suggest close association of bradyarrhythmia occurrence with REM phasic events.


Asp179 in the class A β-lactamase from Mycobacterium tuberculosis is a conserved yet not essential residue due to epistasis.
Conserved residues are often considered essential for function, and substitutions in such residues are expected to have a negative influence on the properties of a protein. However, mutations in a few highly conserved residues of the β-lactamase from Mycobacterium tuberculosis, BlaC, were shown to have no or only limited negative effect on the enzyme. One such mutant, D179N, even conveyed increased ceftazidime resistance upon bacterial cells, while displaying good activity against penicillins. The crystal structures of BlaC D179N in resting state and in complex with sulbactam reveal subtle structural changes in the Ω-loop as compared to the structure of wild-type BlaC. Introducing this mutation in four other β-lactamases, CTX-M-14, KPC-2, NMC-A and TEM-1, resulted in decreased antibiotic resistance for penicillins and meropenem. The results demonstrate that the Asp in position 179 is generally essential for class A β-lactamases but not for BlaC, which can be explained by the importance of the interaction with the side chain of Arg164 that is absent in BlaC. It is concluded that Asp179 though conserved is not essential in BlaC, as a consequence of epistasis.


Effects of clonidine on central and peripheral catecholamine metabolism.
Cerebrospinal fluid (CSF; n = 5) and plasma (n = 7) levels of norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) were examined in abstinent normotensive men with alcohol amnestic disorder during placebo and after 2 wk of clonidine treatment (6 or 12 micrograms/kg/day). Clonidine reduced concentrations of NE and both free and total MHPG in CSF and plasma. The CNS contribution to CSF free MHPG also decreased (as estimated from the differential reductions in CSF and plasma levels). Percent reductions in CSF and plasma NE were substantially greater than those for MHPG, suggesting diminished CNS and peripheral NE release and turnover. CSF levels of homovanillic acid (HVA), which is derived solely from CNS dopamine metabolism, rose in each patient, whereas the CSF serotonin metabolite, 5-hydroxyindoleacetic acid, did not change. Thus the increase in HVA cannot be attributed to inhibition of acid transport from brain to blood. Changes in central noradrenergic and dopaminergic activity correlated inversely; thus diminished NE release and enhanced dopamine metabolism may both contribute to the effects of clonidine in man.


Comparative study of three methods for affinity measurements: capillary electrophoresis coupled with UV detection and mass spectrometry, and direct infusion mass spectrometry.
We present affinity capillary electrophoresis and mass spectrometry (ACE-MS) as a comprehensive separation technique for label-free solution-based affinity analysis. The application of ACE-MS for measuring affinity constants between eight small molecule drugs [ibuprofen, s-flurbiprofen, diclofenac, phenylbutazone, naproxen, folic acid, resveratrol, and 4,4'-(propane-1,3-diyl) dibenzoic acid] and β-cyclodextrin is described. We couple on-line ACE with MS to combine the separation and kinetic capability of ACE together with the molecular weight and structural elucidation of MS in one system. To understand the full potential of ACE-MS, we compare it with two other methods: Direct infusion mass spectrometry (DIMS) and ACE with UV detection (ACE-UV). After the evaluation, DIMS provides less reliable equilibrium dissociation constants than separation-based ACE-UV and ACE-MS, and cannot be used solely for the study of noncovalent interactions. ACE-MS determines apparent dissociation constants for all reacting small molecules in a mixture, even in cases when drugs overlap with each other during separation. The ability of ACE-MS to interact, separate, and rapidly scan through m/z can facilitate the simultaneous affinity analysis of multiple interacting pairs, potentially leading to the high-throughput screening of drug candidates.


Subglacial lake drainage detected beneath the Greenland ice sheet.
The contribution of the Greenland ice sheet to sea-level rise has accelerated in recent decades. Subglacial lake drainage events can induce an ice sheet dynamic response--a process that has been observed in Antarctica, but not yet in Greenland, where the presence of subglacial lakes has only recently been discovered. Here we investigate the water flow paths from a subglacial lake, which drained beneath the Greenland ice sheet in 2011. Our observations suggest that the lake was fed by surface meltwater flowing down a nearby moulin, and that the draining water reached the ice margin via a subglacial tunnel. Interferometric synthetic aperture radar-derived measurements of ice surface motion acquired in 1995 suggest that a similar event may have occurred 16 years earlier, and we propose that, as the climate warms, increasing volumes of surface meltwater routed to the bed will cause such events to become more common in the future.


Study of nanoemulsions using carvacrol/MCT-(Oleic acid-potassium oleate)/ Tween 80 ®- water system by low energy method.
Carvacrol is studied in different fields due to its microbial and antioxidant properties. Its use is limited because of the water insolubility and its strong taste. To overcome these problems, carvacrol has been successfully loaded into nanoemulsions. The low-energy emulsification method Phase Inversion Composition (PIC) is used to prepare oil-in-water nanoemulsions in the carvacrol/medium chain triglycerides (MCT)-(oleic acid-potassium oleate/Tween 80 ®)-water system. Oleic acid acts as a co-surfactant when it is neutralized with KOH along the emulsification path changing the spontaneous curvature of the interface when increasing the HLB number from 1 for the oleic acid to 20 for the potassium oleate and, therefore, changing the HLB number of the surfactant mixture. The phases diagrams are studied in order to understand the behaviour of the system and to establish the composition range where nanoemulsions can be obtained. Nanoemulsions are formed when the emulsification path crosses a region of direct or planar structure without excess of oil. Experimental design is performed in order to study the influence of composition variables as carvacrol/MCT ratio and (oleic-oleate)/Tween 80 ® ratio (OL-OT/T80 ratio) on the diameter of the nanoemulsions and their stability. It has been observed the importance of the HLB number of the surfactants mixture in order to obtain small-sized stable nanoemulsions. Surface response graphic shows that (OL-OT)/T80 ratio is a significant parameter in the mean diameter of the nanoemulsions. A minimum diameter is obtained for a (OL-OT)/T80 ratio 45/55 due to the fact that ratio is near the preferred HLB of the oil mixture and the emulsification path contains a wide liquid crystal monophasic region with all the oil incorporated in the structure. Diameters of 19 nm for carvacrol/MCT ratio of 30/70 or diameters of 30 nm for ratios of 45/55 with high stability values presented a good potential to be incorporated into edible films in the future. Regarding nanoemulsions stability an optimum value is also observed for a carvacrol/MCT ratio. The addition of another carrier oil as olive oil instead of MCT showed an improvement of the nanoemulsions stability against Ostwald ripening, probably due to the smaller solubility of olive oil. The use of olive oil does not significantly change the diameter of the nanoemulsion.


Computational Modeling of Interfacial Behaviors in Nanocomposite Materials.
Towards understanding the bulk material response in nanocomposites, an interfacial zone model was proposed to define a variety of material interface behaviors (e.g. brittle, ductile, rubber-like, elastic-perfectly plastic behavior etc.). It also has the capability to predict bulk material response though independently control of the interface properties (e.g. stiffness, strength, toughness). The mechanical response of granular nanocomposite (i.e. nacre) was investigated through modeling the "relatively soft" organic interface as an interfacial zone among "hard" mineral tablets and simulation results were compared with experimental measurements of stress-strain curves in tension and compression tests. Through modeling varies material interfaces, we found out that the bulk material response of granular nanocomposite was regulated by the interfacial behaviors. This interfacial zone model provides a possible numerical tool for qualitatively understanding of structure-property relationships through material interface design.


High-density lipoproteins reduce palmitate-induced cardiomyocyte apoptosis in an AMPK-dependent manner.
Palmitate has been implicated in the induction of cardiomyocyte apoptosis via reducing the activity of 5' AMP-activated protein kinase (AMPK). We sought to evaluate whether high-density lipoproteins (HDLs), known for their cardioprotective features and their potential to increase AMPK activity, can reduce palmitate-induced cardiomyocyte apoptosis and whether this effect is AMPK-dependent. Therefore, cardiomyocytes were isolated from adult Wistar rat hearts via perfusion on a Langendorff-apparatus and cultured in free fatty acid-free BSA control medium or 0.5 mM palmitate medium in the presence or absence of HDL (5 μg protein/ml) with or without 0.1 μM of the AMPK-inhibitor compound S for the analysis of Annexin V/propidium, genes involved in apoptosis and fatty acid oxidation, and cardiomyocyte contractility. We found that HDLs decreased palmitate-induced cardiomyocyte apoptosis as indicated by a reduction in Annexin V-positive cardiomyocytes and an increase in Bcl-2 versus Bax ratio. Concomitantly, HDLs increased the palmitate-impaired expression of genes involved in fatty acid oxidation. Furthermore, HDLs improved the palmitate-impaired cardiomyocyte contractility. All effects were mediated in an AMPK-dependent manner, concluding that HDLs reduce palmitate-induced cardiomyocyte apoptosis, resulting in improved cardiomyocyte contractility through a mechanism involving AMPK.


Effect of temperature on the unfavorable mixing between tetraethylene glycol dodecyl ether and Pluronic P103.
The fluorescence measurements of tetraethylene glycol dodecyl ether (C12E4) and triblock polymer (Pluronic P103), poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), (EO)17(PO)60(EO)17, binary mixtures have been performed over the whole mixing range in the temperature range of 20-40 degrees C. The results have been evaluated by computing various micellar parameters and excimer formation. It has been concluded that mixed micelle formation takes place due to unfavorable mixing at lower temperature range, and the magnitude of which decreases with the increase in temperature up to 40 degrees C. The reduction in the unfavorable mixing has been attributed to the dehydration of P103 micelles with the increase in temperature.


Retrospective testing of respiratory specimens for COVID-19 to assess for earlier SARS-CoV-2 infections in Alberta, Canada.
The first case of coronavirus disease 2019 (COVID-19) in Alberta, Canada, was confirmed on March 5, 2020. Because the virus testing criteria had changed significantly over this time period, we wanted to ascertain whether previous cases of COVID-19 had been missed in the province. Our aim was to retrospectively evaluate specimens submitted for respiratory virus testing from December 1, 2019, through March 7, 2020, for undetected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections before the first confirmed case. Testing of 23,517 samples (representing 23,394 patients) identified 1 patient positive for SARS-CoV-2. This specimen was collected on February 24, 2020, from a patient with symptoms consistent with COVID-19 who had recently returned from the western United States. Phylogenetic analysis confirmed this viral isolate belonged to lineage B.1. The epidemiology of this case is consistent with those of other early cases before sustained community transmission, which included a travel history outside of Canada. This exercise provides support that local public health pandemic planning was satisfactory and timely.


Optical coherence tomography (OCT) measurements and cognitive performance in multiple sclerosis: a systematic review and meta-analysis.
Several studies report mixed associations between the retinal nerve fiber layer (RNFL) thickness with cognitive and physical disability in persons with multiple sclerosis (PwMS). Systematic synthesis of these findings is crucial in deriving credible conclusions. Five databases were searched from their inception to March 2022. The inclusion criteria for studies were MS-specific and required RNFL and cognitive performance data in order to be analyzed. The selection processes followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The systematic review yielded 31 studies that investigated the association between RNFL thickness and cognitive performance. Twenty-two studies reported positive associations, and nine did not. The meta-analysis included 11 studies with a total of 782 PwMS with mean age of 40.5 years, mean Expanded Disability Status Scale (EDSS) of 2.7, and disease duration of 11.3 years. RNFL thickness was significantly associated Symbol Digit Modalities Test (pooled r = 0.306, p < 0.001), Paced Auditory Serial Addition Test (pooled r = 0.374, p < 0.001) and Word List Generation (WLG, pooled r = 0.177, p < 0.001). RNFL was also significantly correlated with visuospatial learning and memory tests (pooled r = 0.148, p = 0.042) and verbal learning and memory tests (pooled r = 0.245, p = 0.005). Within three eligible studies, no significant association between ganglion cell inner-plexiform layer and SDMT 0.083 (95% CI - 0.186, 0.352) was noted. The heterogeneity was high in all correlation studies (I2 > 63% and p < 0.008) except for the WLG and visuospatial memory findings. RNFL thickness is associated with cognitive processing speed, verbal learning and memory, visual learning and memory, as well as verbal fluency in PwMS. The number of studies included in the meta-analyses were limited due to non-standardized reporting.


Trends in hip fracture incidence and in the prescription of antiosteoporosis medications during the same time period in Belgium (2000-2007).
To examine the secular trend of hip fracture incidence in Belgium between 2000 and 2007 and the concomitant change in the prescriptions of antiosteoporosis medications. The incidence of hip fractures and the number of prescriptions were determined using national databases. A logistic regression including years and 5-year age range was performed to assess the secular trend of hip fracture incidence, and Pearson's correlation coefficient was calculated to examine the relationship between hip fracture incidence and the prescriptions of antiosteoporosis medications. The annual number of hip fractures increased in Belgium from 13,512 in 2000 to 14,744 in 2007, with a more marked increased in men (20.4%) than in women (5.7%). The age-adjusted incidence of hip fractures was significantly decreased by 1.12% per year in women, but declined nonsignificantly by 0.34% per year in men. An increase in the prescriptions of antiosteoporosis medications in women was observed during the same time period. Despite an increase in the number of hip fractures in Belgium between 2000 and 2007, there was a significant decrease in age-adjusted incidence in women but not in men. Although our results suggest that the decrease may be related to the extent of antiosteoporosis medications, a causal relationship cannot be ascertained and many other factors may have contributed to the decrease in age-adjusted incidence.


A facile electrochemical approach to fabricate a nanoporous gold film electrode and its electrocatalytic activity towards dissolved oxygen reduction.
A nanoporous gold film (NPGF) was prepared onto a gold electrode surface using a facile and green electrochemical approach via anodization at 2.0 V in 0.5 mol L(-1) H2SO4. The as-synthesized NPGF electrode showed superior electrocatalytic activity towards dissolved oxygen reduction at a low overpotential (-0.045 V) along with 2-fold enhanced sensitivity.


Correlation between neutrophil to lymphocyte ratio and overactive bladder in South Korean women: a community-based, cross-sectional study.
Many women with overactive bladder (OAB) do not seek medical care despite urinary symptoms. As the diagnosis and treatment of OAB are often late, there is a need to identify undiagnosed OAB patients and start effective treatment. Furthermore, an objective and appropriate screening biomarker for OAB is needed. This study aimed to investigate the relationship between serum neutrophil-to-lymphocyte ratio (NLR) and OAB in South Korean women. Cross-sectional, retrospective study. Jeju National University Hospital. This study included a total of 4394 women (mean age=48.6 years) who underwent self-referred health screenings. Blood tests were conducted and the NLR was calculated by dividing the number of neutrophils by the number of lymphocytes. The severity of OAB was evaluated using the OAB Symptom Score (OABSS). Approximately 9.8% of participants (n=432) were diagnosed with OAB. The association pattern between the NLR and urinary tract symptoms was variable; however, NLR was associated with OAB, by the OABSS and OAB severity (p<0.001). The NLR had a significant relationship with OAB after age, body mass index, homoeostatic model assessment for insulin resistance, 25-hydroxyvitamin D, stress status, and medication for hypertension (OR 1.19, 95% CI 1.06 to 1.32) were adjusted. Elevated NLR is associated with OAB; hence, NLR may be a cost-effective and readily available biomarker of OAB in women.


Consumption of common illicit drugs in twenty-one cities in southwest China through wastewater analysis.
Wastewater-based epidemiology (WBE) was applied to estimate illicit drugs consumption at a provincial scale in southwest China. A large-scale wastewater sampling campaign was carried out from October to November in 2021 in 156 different wastewater treatment plants (WWTPs). Two 24-h composite influent wastewater samples were collected in each WWTP. Concentrations of 11 illicit drugs or their metabolites were determined using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Benzoylecgonine, cocaine, 6-monoacetylmorphine, norketamine, 3,4-methylenedioxymethamphetamine (MDMA), and MDA were not detected in any of the wastewater samples. Methamphetamine and morphine were detected in >84% of samples, while ketamine was found in about 6% of the samples. The city-specific population-weighted consumption of methamphetamine and ketamine were in the range of 0.6-49.7 and N.D.-7.0 mg 1000 inh-1 day-1, respectively, with provincial population-weighted values of 22.6 and 2.4 mg 1000 inh-1 day-1 in southwest China. The city-specific load of morphine varied from 3.2 to 10.2 mg 1000 inh-1 day-1, with provincial population-weighted load of 6.7 mg 1000 inh-1 day-1. Taking into account therapeutic use of morphine and codeine, the provincial heroin consumption was estimated to be 10.3 mg 1000 inh-1 day-1, ranging from 1.7 to 18.5 mg 1000 inh-1 day-1 in 21 cities. Overall, the patterns of illicit drugs use were similar across southwest China, with high prevalence of methamphetamine and heroin, but relatively low use of ketamine. These findings could provide accurate drugs consumption information for timely identifying potential hotspots of illicit drugs use in southwest China.


Regulation of nickel-induced T-cell responsiveness by CD4+CD25+ cells in contact allergic patients and healthy individuals.
In this study, we investigated the capacity of CD4+CD25+ regulatory T cells to suppress nickel-specific effector T cells, both in nickel-allergic patients and healthy controls. CD4+ cells isolated from allergic patients showed an increased proliferative response to nickel, whereas CD4+ cells from negative controls did not respond to allergen. When CD4+CD25+ cells were depleted, nickel-specific responsiveness was strongly increased both in allergic and in non-allergic individuals, with the most pronounced effect in allergic patients. These regulatory T cells were anergic to nickel but inhibited nickel-specific CD4+CD25- effector T cells in coculture experiments. CD4+CD25+ cells from nickel-allergic patients showed only a limited capacity to suppress effector T-cell responsiveness, because an increased nickel reactivity could still be detected in these cocultures. None of the isolated CD4+CD25+ cells, either isolated from healthy controls or allergic patients, produced IL-10 in response to nickel. Overall, these results support the view that CD4+CD25+ cells can control the activation of nickel-specific effector T cells in non-allergic individuals, whereas this regulatory capacity is impaired in allergic patients. To investigate the presence of allergen-specific regulatory T cells in truly naïve, non-sensitized individuals, T-cell reactivity should also be studied with non-environmental contact allergens, such as para-phenylenediamine.


Ultrasound assisted formation of essential oil nanoemulsions: Emerging alternative for Culex pipiens pipiens Say (Diptera: Culicidae) and Plodia interpunctella Hübner (Lepidoptera: Pyralidae) management.
Over the last years, nanotechnology has contributed to the development of new botanical insecticides formulations based on essential oils (EO), which are safe for the human health and the environment. Nanoemulsions (NEs) can enhance the bioactivity of the EO to prevent the premature volatility and degradation of the active ingredients. In our work, geranium EO (Geranium maculatum L.) was used to develop micro and nanoemulsions adding Tween 80 as surfactant. For NEs formulation, ultrasound was applied and the physicochemical and ultrasound parameters were optimized: oil: surfactant ratio = 1:2, ultrasound power = 65 W, sonication time = 2 min, cycles = 30 on/20 off and ultrasonic probe distance = 3.7 cm. The NEs obtained had 13.58 nm and polydisperse index (PDI) values of 0.069. They were stored at 25 °C and were stable for 60 days. The present study also demonstrated the potential of NEs to enhance the toxicity of geranium EO against larvae of Culex pipiens pipiens (EO LC50 = 80.97 ppm, NEs LC50 = 48.27 ppm) and Plodia interpunctella (EO + β-cypermethrin LD50 = 0.16 μg larvae-1, NEs + β-cypermethrin LD50 = 0.07 μg larvae-1). Overall, our findings pointed out that NEs can increase twofold the insecticidal efficacy of EO, and thus, they can be considered further for the development of botanical insecticides.


Enzyme-amplified receptor assay screening test for chlorpromazine, trifluoperazine, and phencyclidine.
A new receptor based assay is described for the determination of classes of drugs which have high affinities for the acetylcholine receptor. The method is based upon the inhibition of the enzyme activity of an enzyme-drug conjugate by the binding to the receptor protein, and competition between free drugs and the enzyme-drug conjugate for a limited number of receptor sites. The activity of the enzyme marker system, glucose-6-phosphate dehydrogenase covalently conjugated to desipramine, is monitored by colorimetric detection of the rate of NADH formation at 340 nM. The procedure proposed is designed to provide a simple drug screen which can be done in a minimally equipped laboratory while achieving the required sensitivity. The technique is illustrated for three acetylcholine channel binding compounds: the hallucinogen phencyclidine (PCP) and the antipsychotic agents chlorpromazine and trifluoperazine. This procedure yields calibration curves with detection limits at nanomolar levels of drug, with binding responses dependent on the amounts of receptor and enzyme-labeled drug used. Aspecific binding responses of unlabeled enzyme to drug or receptor to compounds with low affinity for the receptor are shown to have minimal effect on the assay.


The accuracy of single-seed dose superposition for I-125 implants.
The Monte Carlo method was used to study perturbations of single I-125 seed dose distributions created by the presence of one or three neighboring seeds for the case of seeds immersed in a water phantom. Perturbation factors were determined within the geometric shadow of neighboring seeds for two-seed designs, four-seed spacings, and several choices of dose point. The results were compared to dose estimates obtained by the simple superposition of single-seed data for one- and two-plane implants. Some significant differences were found.


Epigenetic drivers and genetic passengers on the road to cancer.
Cancer is traditionally viewed as a primarily genetic disorder, however it is now becoming accepted that cancer is also a consequence of abnormal epigenetic events. Genetic changes and aneuploidy are associated with alterations in DNA sequence, and they are a hallmark of the malignant process. Epigenetic alterations are universally present in human cancer and result in heritable changes in gene expression and chromatin structure over many cell generations without changes in DNA sequence, leading to functional consequences equivalent to those induced by genetic alterations. Importantly, intriguing evidence emerged suggesting that epigenetic changes may precede and provoke genetic changes. In this scenario, epigenetic events are primary events while genetic changes (such as mutations) may simply be a consequence of disrupted epigenetic states. This fact may explain why many genetic screens proved to be limited with regard to cancer causality and pathogenesis. Aberrant epigenetic events affect multiple genes and cellular pathways in a non-random fashion and this can predispose to induction and accumulation of genetic changes in the course of tumour initiation and progression. These considerations are critical for a better understanding of tumourigenesis and molecular events underlying the acquisition of drug resistance, as well as development of novel strategies for cancer therapy and prevention.


Dataset of quantification and classification of microplastics in Mexican sandy beaches.
The presence of microplastics in marine and coastal environments is an issue of concern for the preservation of these ecosystems. This dataset provides the results of the first national assessment of the presence of microplastics (<5 mm) in Mexican beaches. The research included 35 beaches along the five marine regions of the country. For each beach, ten samples (19 cm diameter, 5 cm depth) were taken along the high-tide line, and then microplastics were extracted by flotation and sieving. All the plastic particles were quantified and classified based on their colour, type of particle, and type of plastic used in their production, using visual inspection and FTIR spectroscopy. The use of the same methodology in all the beaches allowed us to compare and analyze the results, which are reported in the article Microplastics in Mexican beaches.


An overview of Fructus Meliae Toosendan: Botany, traditional uses, phytochemistry, pharmacology and toxicology.
Fructus Meliae Toosendan (FMT) is the dried and mature fruit of MeLia toosendan Sieb.et Zucc. It contains a variety of chemical constituents and reported to possess a variety of pharmacological activities. This review aims to provide a thorough and organized summary of botany, traditional uses, chemical ingredients, pharmacological actions, toxicity, quality control, and uses. In this review, we have compiled the data regarding FMT from 1994 to 2022 in the databases: Web of Science, PubMed, Google Scholar, CNKI, and Baidu Scholar. The keywords: "Fructus Meliae Toosendan", "botany", "traditional uses","chemical components", "pharmacological activity", "toxicity", "quality control" and "clinical application" have been used to collected the literature published in the online bibliographic databases. Based on the correlation of these documents and FMT, 126 articles were finally selected as references. This paper provides a reasonable summary of the 190 chemical components of FMT and its pharmacological effects and toxicity. Moreover, this paper also compiled the quality control studies and clinical applications. In the future, more experimental studies on FMT are needed to achieve the purpose of toxicity reducing and efficacy enhancing. This comprehensive review of FMT can provide a reference for subsequent relevant studies.


TNIP1 is a corepressor of agonist-bound PPARs.
Nuclear receptor (NR) coregulators include coactivators, contributing to holoreceptor transcriptional activity, and corepressors, mediating NR target gene silencing in the absence of hormone. We identified an atypical NR coregulator, TNFα-induced protein 3-interacting protein 1 (TNIP1), from a peroxisome proliferator activated receptor (PPAR) α screen of a human keratinocyte cDNA library. TNIP1's complex nomenclature parallels its additional function as an NF-κB inhibitor. Here we show TNIP1 is an atypical NR corepressor using two-hybrid systems, biochemical studies, and receptor activity assays. The requirements for TNIP1-PPAR interaction are characteristic for coactivators; however, TNIP1 partially decreases PPAR activity. TNIP1 has separable transcriptional activation and repression domains suggesting a modular nature to its overall effect. It may provide a means of lowering receptor activity in the presence of ligand without total loss of receptor function. TNIP1's multiple roles and expression in several cell types suggest its regulatory effect depends on its expression level and the expression of other regulators in NR and/or NF-κB signaling pathways. As a NR coregulator, TNIP1 targeting agonist-bound PPAR and reducing transcriptional activity offers control of receptor signaling not available from typical corepressors and may contribute to combinatorial regulation of transcription.


Comparison of pneumatic displacement for submacular hemorrhages with gas alone and gas plus tissue plasminogen activator.
To retrospectively evaluate efficacy, safety, and visual outcomes of pneumatic displacement for submacular hemorrhages (SMHs) with or without tissue plasminogen activator (tPA). Sixty-eight eyes with fresh SMHs underwent pneumatic displacement. Thirty eyes received intravitreal injection of pure C3F8 gas alone and 38 eyes received gas with tPA (25 μg). The visual analog scale was used to evaluate displacement. The main outcome measures were the visual analog scale score and best-corrected visual acuity 1 month after treatment. The efficacy and safety of tPA were evaluated. The visual analog scale score was 4.9 ± 2.5 in the gas group and 5.9 ± 2.9 in the gas plus tPA group. Sixteen eyes (53.3%) in the gas group and 15 eyes (39.5%) in the gas plus tPA group had best-corrected visual acuity improvements. In the gas group, complications included retinal detachment (n = 1, 3.3%), vitreous opacity (n = 7, 23.3%), and rebleeding (n = 1, 3.3%). In the gas plus tPA group, vitreous opacity (n = 6, 15.8%) was the only complication. Overall, both groups had similar displacement of SMH, visual improvement, and complication rates at 1 month. Intravitreal injection of pure C3F8 gas displaced SMHs and improved best-corrected visual acuity in eyes with SMHs. No adjuvant effect or adverse reactions of tPA were found.


Photolysis of CBr4 and its transient solvent stabilized (CBr3+//Br-)solv ion pair.
In this paper we describe the mechanism of the photodissociation of CBr4 in various solvents. We have monitored and identified the intermediate species and determined the growth and decay rates of the excited states and metastable species formed during the photodissociation process by means of ultrafast time-resolved spectroscopy. On the basis of the experimental data presented in this paper, the observed transient spectra and species have been assigned to the stabilized solvated ion pair (CBr3+//Br-)solv.


Ampullary adenoma: clinical manifestations, diagnosis, and treatment.
Ampullary adenomas occur sporadically and in the setting of familial polyposis syndromes. In either case, and whether symptomatic at presentation or found asymptomatically in the setting of endoscopic screening programs, they are premalignant lesions with risk for malignant degeneration to carcinoma following the adenoma-to-carcinoma sequence that is well recognized in colonic adenocarcinoma. Accordingly, many experts advocate excision, although others cite the low rate of histologic progression suggested by some recent studies as justification for close endoscopic surveillance rather than excision before demonstration of dysplastic change. This recommendation, however, is complicated by considerable data underscoring the limited accuracy of endoscopic forceps biopsy in detecting occult foci of carcinoma within ampullary adenoma. Thus, the optimal management of these lesions continues to generate considerable controversy. Indications for excision of an ampullary adenoma include treatment of immediate symptoms as well as prevention of malignant degeneration. Although pancreaticoduodenectomy has long been considered the standard procedure for ampullary carcinoma, much controversy exists regarding the procedure of choice for ampullary adenoma. Radical surgery (pancreaticoduodenectomy) possesses the advantage of low recurrence rate but at the expense of higher morbidity (25%-65%) and mortality (0%-10%). Local surgical excision (surgical ampullectomy) possesses the advantages of lower morbidity (0%-25%), essentially nil mortality, and possibly decreased length of hospital stay, but decidedly higher recurrence rates (generally 5%-30%) and the need for postoperative endoscopic surveillance. Snare ampullectomy is a newer endoscopic excisional technique for which limited data are available; advantages compared with radical surgery mirror those of local surgical excision, with apparent lower mortality (0%-1%) and lower morbidity (12%). Presumed advantages compared with local surgical excision include lack of necessity for general anesthesia and laparotomy with comparable morbidity. Disadvantages seem to include limited availability of experienced operators, procedural complexity sometimes requiring adjunctive modalities such as fulguration, the need for multiple procedures (mean, 2.0 procedures) to effect complete excision, and recurrence rates approaching 30%, with a requirement for continued endoscopic surveillance. Ultimately, choice is driven by availability of local expertise, patient tolerance of or expected compliance with long-term endoscopic surveillance programs, presence or absence of coexisting familial polyposis syndromes, medical comorbidities, and overall life expectancy.


Auditory sensitivity of larval zebrafish (Danio rerio) measured using a behavioral prepulse inhibition assay.
Zebrafish (Danio rerio) have become a valuable model for investigating the molecular genetics and development of the inner ear in vertebrates. In this study, we employed a prepulse inhibition (PPI) paradigm to assess hearing in larval wild-type (AB) zebrafish during early development at 5-6 days post-fertilization (d.p.f.). We measured the PPI of the acoustic startle response in zebrafish using a 1-dimensional shaker that simulated the particle motion component of sound along the fish's dorsoventral axis. The thresholds to startle-inducing stimuli were determined in 5-6 d.p.f. zebrafish, and their hearing sensitivity was then characterized using the thresholds of prepulse tone stimuli (90-1200 Hz) that inhibited the acoustic startle response to a reliable startle stimulus (820 Hz at 20 dB re. 1 m s(-2)). Hearing thresholds were defined as the minimum prepulse tone level required to significantly reduce the startle response probability compared with the baseline (no-prepulse) condition. Larval zebrafish showed greatest auditory sensitivity from 90 to 310 Hz with corresponding mean thresholds of -19 to -10 dB re. 1 m s(-2), respectively. Hearing thresholds of prepulse tones were considerably lower than previously predicted by startle response assays. The PPI assay was also used to investigate the relative contribution of the lateral line to the detection of acoustic stimuli. After aminoglycoside-induced neuromast hair-cell ablation, we found no difference in PPI thresholds between treated and control fish. We propose that this PPI assay can be used to screen for novel zebrafish hearing mutants and to investigate the ontogeny of hearing in zebrafish and other fishes.


Delineation of a toxin-encoding segment of a Bacillus thuringiensis crystal protein gene.
Crystals of Bacillus thuringiensis subsp. kurstaki HD-1-Dipel contain a Mr 134,000 protoxin which can be cleaved by proteolysis to a peptide of Mr approximately 70,000; this peptide is lethal to lepidopteran larvae. We have analyzed the peptides produced by recombinant Escherichia coli strains bearing deletions and fusions of the protoxin gene in order to delineate the portion of the gene which encodes the toxic peptide. The recombinant strains produced the toxic peptide as well as larger peptides whose size was related to the length of the deleted gene. The results indicate that the amino-terminal 55% of the protoxin protein is sufficient for toxicity. While two different gene fusions to the 10th codon allowed the synthesis of toxic polypeptides, fusions to the 50th codon did not. 3' end deletions up to the 645th codon allowed synthesis of the toxic peptide whereas a deletion to the 603rd codon yielded a non-toxic peptide. Some of the 5' and 3' end alterations to the gene caused changes in the proteolytic cleavage patterns of the polypeptides synthesized by E. coli, suggesting that the alterations led to conformational changes in the proteins. The presence of different 3' end segments affected the levels of synthesis of the altered crystal proteins.


KpsF is the arabinose-5-phosphate isomerase required for 3-deoxy-D-manno-octulosonic acid biosynthesis and for both lipooligosaccharide assembly and capsular polysaccharide expression in Neisseria meningitidis.
We have identified and defined the function of kpsF of Neisseria meningitidis and the homologues of kpsF in encapsulated K1 and K5 Escherichia coli. KpsF was shown to be the arabinose-5-phosphate isomerase, an enzyme not previously identified in prokaryotes, that mediates the interconversion of ribulose 5-phosphate and arabinose 5-phosphate. KpsF is required for 3-deoxy-d-manno-octulosonic acid (Kdo) biosynthesis in N. meningitidis. Mutation of kpsF or the gene encoding the CMP-Kdo synthetase (kpsU/kdsB) in N. meningitidis resulted in expression of a lipooligosaccharide (LOS) structure that contained only lipid A and reduced capsule expression in the five invasive disease-associated meningococcal serogroups (A, B, C, Y, and W-135). The step linking meningococcal capsule and LOS biosynthesis was shown to be Kdo production as the expression of capsule was wild type in a Kdo transferase (kdtA) mutant. Thus, in addition to lipooligosaccharide assembly, Kdo is required for meningococcal capsular polysaccharide expression. Furthermore, N. meningitidis, unlike enteric Gram-negative bacteria, can survive and synthesize only unglycosylated lipid A.


Atypical Neurogenesis in Induced Pluripotent Stem Cells From Autistic Individuals.
Autism is a heterogeneous collection of disorders with a complex molecular underpinning. Evidence from postmortem brain studies have indicated that early prenatal development may be altered in autism. Induced pluripotent stem cells (iPSCs) generated from individuals with autism with macrocephaly also indicate prenatal development as a critical period for this condition. But little is known about early altered cellular events during prenatal stages in autism. iPSCs were generated from 9 unrelated individuals with autism without macrocephaly and with heterogeneous genetic backgrounds, and 6 typically developing control individuals. iPSCs were differentiated toward either cortical or midbrain fates. Gene expression and high throughput cellular phenotyping was used to characterize iPSCs at different stages of differentiation. A subset of autism-iPSC cortical neurons were RNA-sequenced to reveal autism-specific signatures similar to postmortem brain studies, indicating a potential common biological mechanism. Autism-iPSCs differentiated toward a cortical fate displayed impairments in the ability to self-form into neural rosettes. In addition, autism-iPSCs demonstrated significant differences in rate of cell type assignment of cortical precursors and dorsal and ventral forebrain precursors. These cellular phenotypes occurred in the absence of alterations in cell proliferation during cortical differentiation, differing from previous studies. Acquisition of cell fate during midbrain differentiation was not different between control- and autism-iPSCs. Taken together, our data indicate that autism-iPSCs diverge from control-iPSCs at a cellular level during early stage of neurodevelopment. This suggests that unique developmental differences associated with autism may be established at early prenatal stages.


Effect of two fascial incision options for access to the temporomandibular joint on facial nerve function: objective investigation.
This study was performed to compare the effects on facial nerve (FN) function of the deep supra-temporalis muscle subfascial approach (DSFA) and traditional fascial approach (TFA) for access to the temporomandibular joint (TMJ), via qualitative and quantitative evaluations. Thirty patients requiring open TMJ surgery were randomly allocated to one of two groups: group A patients underwent the DSFA approach, while group B patients underwent the TFA approach. The TMJ was accessed via modified endaural incision with temporal extension. Clinical examinations, FN conduction tests, and electromyography (EMG) of the frontalis and orbicularis oculi muscles were used to assess FN function. A FN function deficit was noted in 50% of the whole sample population immediately after surgery, with no statistically significant difference between the groups (P = 0.082). Overall, 37.5% of the total study population experienced temporary loss of frontalis muscle activity, while zygomatic nerve injury was seen only in 25% of group A. Within 2-6 months, normal function returned in both groups. Nerve conduction studies showed no statistically significant difference between the groups in terms of nerve amplitude or latency after surgery. However, EMG of orbicularis oculi activity showed a significant difference between the groups after 6 months (P = 0.010). The results suggest that the traditional dissection approach is more protective of the FN, especially the zygomatic branch, than the deeper dissection technique.


Facilitators and barriers to person-centered planning from the perspectives of individuals receiving medicaid home and community-based services and care managers.
While person-centered planning is required within Medicaid Home and Community-Based Services (HCBS) programs, we know little about the extent to which it is being implemented and best approaches to measuring quality. Our study explored the experiences of individuals receiving Medicaid HCBS and care managers facilitating person-centered planning in three states to learn from their perspectives of facilitators and barriers. We partnered with a national health plan and affiliated health plans in three states for recruitment. We used a semi-structured interview guide to conduct remote interviews with 13 individuals receiving HCBS and 31 care managers. To triangulate our findings, we reviewed assessment instruments from the three states and the person-centered care plans of HCBS recipients. From the perspectives of individuals receiving HCBS, facilitators to person-centered planning included: choice and control, personal goals and strengths, and relational communication. Care managers similarly identified the importance of relational communication, but also identified the development of measurable goals. Barriers from the perspectives of individuals receiving HCBS included: medical orientation of care plan, administrative and systemic barriers, and competencies of care managers. Care managers similarly identified administrative and systemic barriers. This exploratory study provides important perspectives on implementation of person-centered planning. Findings can help inform improvements in policy and practice, as well as guide future directions in quality measure development and assessment.


Short-term outcome and complications following cutaneous reconstruction using cranial superficial epigastric axial pattern flaps in dogs: six cases (2008-2022).
To investigate short-term outcome and complications following the use of the cranial superficial epigastric axial pattern flap to reconstruct cutaneous defects in dogs. Medical records from dogs undergoing reconstructive surgery between 2008 and 2022 by means of cranial superficial epigastric axial pattern flap were reviewed. Data on signalment, reason for reconstruction, defect size, flap healing, post-operative complications and need for revision surgery were collected. Six dogs were included in the study. Indications for reconstruction included neoplasia (4/6), skin necrosis due to vehicular trauma (1/6) and dog bite (1/6). Postoperative complications occurred in 50% of the patients and included seroma (1/6), bruising (2/6) and necrosis of the distal portion of the flap (2/6), with two dogs developing concurrent complications. One dog required open wound management and additional surgery. Overall outcome was scored excellent in three, good in two, and fair in one dog. Despite the relatively high complication rate, most of the complications were deemed minor and could be managed conservatively. Eventually, all wounds healed completely and only one flap required revision surgery.


Focal spots of size lambda/23 open up far-field fluorescence microscopy at 33 nm axial resolution.
We report spots of excited molecules of 33 nm width created with focused light of lambda = 760 nm wavelength and conventional optics along the optic axis. This is accomplished by exciting the molecules with a femtosecond pulse and subsequent depletion of their excited state with red-shifted, picosecond-pulsed, counterpropagating, coherent light fields. The lambda/23 ratio constitutes what is to our knowledge the sharpest spatial definition attained with freely propagating electromagnetic radiation. The sub-diffraction spots enable for the first time far-field fluorescence microscopy with resolution at the tens of nanometer scale, as demonstrated in images of membranes of bacillus megaterium.


Staged repair of interrupted aortic arch with ventricular septal defect compared with primary repair in infancy.
Interrupted aortic arch is a poor prognosis cardiac anomaly with nearly 100 percent mortality if not recognized and treated early. The associated intracardiac lesions often lead to death if only the arch defect is repaired. Several recent reports have described patients with interrupted aortic arch who were treated as infants by primary repair of the arch defect with simultaneous repair of the intracardiac lesions. The improved survival data from these series have been attributed to the simultaneous repair of both lesions. We report herein on nine patients with both interrupted aortic arch and ventricular septal defect seen at Children's Hospital and Medical Center in Seattle from 1979 to 1987. Three patients had partial expression of DiGeorge's syndrome. All patients underwent primary repair of the interrupted aortic arch with concomitant pulmonary artery banding during infancy (mean age 18 days, range 2 days to 4 months). Operative mortality was 11 percent (1 of 9 patients). Eight patients had eventual repair of the ventricular septal defect (mean age 18 months, range 6 to 29 months) with one death occurring at 5 months postoperatively (12 percent mortality). The overall mortality of these nine patients was 22 percent. Staged repair of interrupted aortic arch with associated ventricular septal defect can be performed with results comparable to simultaneous primary repair in infancy. The improved survival from either approach is more likely to be attributable to improved perioperative stabilization, particularly the use of prostaglandin E.


Understanding Factors that Influence Health Care Utilization Among Mixtec and Zapotec Women in a Farmworker Community in California.
This paper examines health care utilization among indigenous immigrants from Oaxaca, Mexico, who have settled in a farmworker community in southern California. In 2016, two trained Spanish-Mixteco and Spanish-Zapoteco bi-lingual interviewers conducted in-depth interviews with 44 indigenous women residing in Oxnard, California on issues that affect health care utilization. Interviews were conducted in Mixteco, Zapoteco and Spanish and were coded to identify structural, cultural, and provider-related barriers to health care utilization. Five bi-lingual Spanish-Mixteco indigenous interpreters employed at local clinics were also interviewed. Many women reported lack of health insurance, inability to pay, language barriers, long waiting times, rushed encounters with providers, and seeking western medical care only after home remedies did not work. However, several women were able to access routine health care services, often with support from indigenous interpreters employed at clinics. Interviews with five interpreters found that they provided assistance with interpretation during medical encounters and appointment making. They also educated patients about upcoming exams, identified low-cost services and insurance programs available to patients, assisted with paperwork and occasionally educated physicians on behalf of their patients. In addition to addressing barriers to health care access our findings suggest the importance of identifying and leveraging community assets, such as indigenous navigators, when developing programs for such underserved communities. Our findings can inform best practice in settings that provide health care to indigenous populations and may also apply to settings that provide health care to other immigrant communities that have very limited familiarity and contact with western health care.


TiO2 nanoflower photocatalysts: Synthesis, modifications and applications in wastewater treatment for removal of emerging organic pollutants.
Titanium dioxide (TiO2) has been considered as one of the most promising photocatalysts nanomaterials and is being used in a variety of fields of energy and environment under sunlight irradiation via photocatalysis. Highly efficient photocatalytic materials require the design of the proper structure with excellent morphology, interfacial structures, optical and surface properties, etc. Which are the key points to realize effective light-harvesting for photocatalytic applications. Hierarchical TiO2 based nanoflower structures (i.e., 3D nanostructures) possess such characteristics and have attracted much attention in recent years. The uniqueness of TiO2 nanoflowers (NFs) with a coarse texture and arranged structures demonstrates higher photocatalytic activity. This review deals with the hydrothermal synthesis of 3D TiO2 NFs and effect of shape/size as well as various key synthesis parameters to improve their optoelectronic and photocatalytic properties. Furthermore, to improve their photocatalytic properties, various strategies such as doping engineering and heterojunction/nanocomposite formation with other functional nanomaterials have been discussed followed by their potential applications in photocatalytic degradation of various emerging pollutants discharged into the wastewater from various sources. Importance of such 3D nanoarchitecutres and future research in other fields of current interest in environments are discussed.


[The structure and function of an automated system for predicting neonatal body weight (the Sinodeta P/1)].
The structure and function of an automated nosometric system, created by the authors, for prognosis of the risk of delivery of a child with low weight is described. The system is designed for health services, which give direction to parturient (public health sectors) and obstetric wards without technique and specialists for management of such children. The summarized extract is made on 883 cases, but verification--on 463 cases. The total effectiveness of the system is 82.1% against 66.25% of exact results during intuitive prognosis.


Comparative assessment of image quality for coronary CT angiography with iobitridol and two contrast agents with higher iodine concentrations: iopromide and iomeprol. A multicentre randomized double-blind trial.
To demonstrate non-inferiority of iobitridol 350 for coronary CT angiography (CTA) compared to higher iodine content contrast media regarding rate of patients evaluable for the presence of coronary artery stenoses. In this multicentre trial, 452 patients were randomized to receive iobitridol 350, iopromide 370 or iomeprol 400 and underwent coronary CTA using CT systems with 64-detector rows or more. Two core lab readers assessed 18 coronary segments per patient regarding image quality (score 0 = non diagnostic to 4 = excellent quality), vascular attenuation, signal and contrast to noise ratio (SNR, CNR). Patients were considered evaluable if no segment had a score of 0. Per-patient, the rate of fully evaluable CT scans was 92.1, 95.4 and 94.6 % for iobitridol, iopromide and iomeprol, respectively. Non-inferiority of iobitridol over the best comparator was demonstrated with a 95 % CI of the difference of [-8.8 to 2.1], with a pre-specified non-inferiority margin of -10 %. Although average attenuation increased with higher iodine concentrations, average SNR and CNR did not differ between groups. With current CT technology, iobitridol 350 mg iodine/ml is not inferior to contrast media with higher iodine concentrations in terms of image quality for coronary stenosis assessment. • Iodine concentration is an important parameter for image quality in coronary CTA. • Contrast enhancement must be balanced against the amount of iodine injected. • Iobitridol 350 is non-inferior compared to CM with higher iodine concentrations. • Higher attenuation with higher iodine concentrations, but no SNR or CNR differences.


The challenge of disseminating new medical technologies: treatment of cardiac arrhythmias.
Although new health care technologies and procedures can improve the quality of patient care, payers may be reluctant to pay for them, clinicians must be carefully trained to use them effectively, and primary care physicians must keep track of a vast number of developments to make appropriate referrals. This article illustrates the challenges presented by new technology by discussing the cost-quality-access issues raised by technology developed to diagnose and treat cardiac arrhythmias.


Enhancing measures of ESE to incorporate aspects of place: Personal reputation and place-based social legitimacy.
We argue that existing measures of entrepreneurial self-efficacy (ESE) are underspecified in the context of tight-knit communities, where personal reputation plays a major role. We propose a new place-based ESE dimension that measures assessment by individuals of their ability to elicit respect from their community. This integral ESE component points to the very meaning of entrepreneurship in highly relational contexts. Although our enhanced ESE measure incorporates some influences of place, other aspects, such as geographical context, continue to moderate the relationship between ESE and entrepreneurial aptitude. We conclude with a discussion of the relevance and utility of this enhanced measure.


Ethyl 3-amino-5-bromo-1-benzo-furan-2-carboxyl-ate.
The title compound, C11H10BrNO3, is close to planar with the benzo-furan unit and the ester group subtending a dihedral angle of 5.25 (2)°. The mol-ecular structure features an intra-molecular N-H⋯O inter-action. In the crystal, N-H⋯O hydrogen bonds involving carboxyl O-atom acceptors generate a chain extending along [201].


[Health care of refugees - A short review with focus on infectious diseases].
Few guidelines for health care of refugees exist in Germany. Screening as a part of initial health checks as well as general organisation of early health care for refugees is very heterogenous across different regions. Current experience will be relevant to develop integrated health care models. Prevention and care of infectious diseases are an important part of early health care for refugees, even if non-communicable diseases and mental health conditions should also be considered in every effort to design early health care models. We are presenting a pragmatic review of current evidence for prevention and care of tuberculosis, HIV, chronic viral hepatitis and other infectious diseases. More evidence is needed to assess morbidity and efficacy of early health care interventions and integrated care models in refugees.


The role of TrmB and TrmB-like transcriptional regulators for sugar transport and metabolism in the hyperthermophilic archaeon Pyrococcus furiosus.
TrmB of Pyrococcus furiosus was discovered as the trehalose/maltose-specific repressor for the genes encoding the trehalose/maltose high-affinity ABC transporter (the TM system). TrmB also represses the genes encoding the high affinity maltodextrin-specific ABC transporter (the MD system) with maltodextrin and sucrose as inducers. In addition, TrmB binds glucose leading to an increased repression of both, the TM and the MD system. Thus, TrmB recognizes different promoters and depending on the promoter it will be activated or inactivated for promoter binding by different sugar effectors. The TrmB-like protein TrmBL1 of P. furiosus is a global regulator and recognizes preferentially, but not exclusively, the TGM (for Thermococcales-glycolytic motif) sequence that is found upstream of the MD system as well as of genes encoding enzymes involved in the glycolytic and the gluconeogenic pathway. It responds to maltose and maltotriose as inducers and functions as repressor for the genes encoding the MD system and glycolytic enzymes, but as activator for genes encoding gluconeogenic enzymes. The TrmB-like protein TrmBL2 of P. furiosus lacks the sugar-binding domain that has been determined in TrmB. It recognizes the MD promoter, but not all TGM harboring promoters. It is evolutionary the most conserved among the Thermococcales. The regulatory range of TrmBL2 remains unclear.


Imaging update in spinal tuberculosis.
Tuberculosis is ancient disease known to mankind. Diagnosis and management of spinal tuberculosis has immensely improved in last few decades. Imaging, particularly MRI, plays important role in diagnosis of spinal tuberculosis and its complications. Four common imaging patterns of spinal tuberculosis include paradiscal type, central type, Anterior subligamentous type, and posterior type. Imaging also plays important role in differentiation of spinal tuberculosis from its mimics, particularly pyogenic spondylitis, and metastasis. Radiological interventions, such as CT guided vertebral biopsy, and percutaneous drainage of cold abscess, are commonly used in management of spinal tuberculosis. Monitoring of therapeutic response is often based on clinical evaluation and imaging. MRI is most common imaging modality used. Signs of healing include bony ankylosis, resolution of marrow edema, decrease in contrast enhancement, and fatty change with in bone marrow. PET CT is recently evaluated for response assessment with promising results. This review summarizes pathophysiology, clinical presentation, imaging features, radiological interventions, and response assessment in spinal tuberculosis.


Primary neurilemmal tumour of the liver: case report.
A probably unique case of primary benign neurilemmoma of the liver is presented in which no evidence of visceral neurofibromatosis was observed. The histological characteristic of the tumour are discussed.


Ultra-low-dose and very-low-dose Lupron downregulation protocols for poor responders based on POSEIDON group 3 and 4 classifications.
The objective of this study was to assess if very-low-dose Lupron (VLDL) and ultra-low-dose Lupron (ULDL) protocols can have comparable cycle outcomes when compared to other "poor responder" stimulation protocols based on POSEIDON classification groups 3 (PG3) and 4 (PG4). A retrospective cohort study at a single, large academic center was performed. Women in PG3 (age < 35, AMH < 1.2 ng/mL) or PG4 (age ≥ 35, AMH < 1.2 ng/mL) undergoing in vitro fertilization using an ULDL (Lupron 0.1 to 0.05 mg daily), VLDL (Lupron 0.2 to 0.1 mg daily), microflare (Lupron 0.05 mg twice a day), estradiol priming/antagonist, antagonist, or minimal stimulation protocols from 2012 to 2021 were included. The primary outcome was the number of mature oocytes (MII) obtained. The secondary outcome was live birth rate (LBR). The cohort included 3601 cycles. The mean age was 38.1 ± 3.8 years. In the PG3 group, ULDL and VLDL protocols produced a comparable number of MIIs (5.8 ± 4.3 and 5.9 ± 5.4, respectively) and live births (33.3% and 33.3%, respectively) when compared to other protocols. In the PG4 group, ULDL and VLDL protocols resulted in a higher percentage of MIIs when compared to microflare or minimal stimulation (Microflare/ULDL: adjusted relative risk (aRR) 0.78 (95% CI 0.65, 0.95); min stim/ULDL: aRR 0.47 (95% CI 0.38, 0.58); microflare/VLDL: aRR 0.77 (95% CI 0.63, 0.95); min stim/VLDL: aRR 0.47 (95% CI 0.38, 0.95)). There were no significant differences in LBR. Dilute Lupron downregulation protocols have comparable outcomes to other poor responder protocols and are reasonable to use.


Population norms of health-related quality of life in Moscow, Russia: the EQ-5D-5L-based survey.
To develop population norms for the EQ-5D-5L questionnaire based on a representative sample of Moscow citizens. We used quota sampling accounting for sex, age group and administrative district of residence. Respondents in randomly selected outdoor and indoor locations were surveyed with the official Russian paper-and-pencil version of the EQ-5D-5L questionnaire and a set of socio-demographic questions. We estimated four types of EQ-5D results: the distribution of limitations according to EQ-5D-5L dimensions, the perception of the health-related quality of life (HRQoL) with a visual analogue scale (EQ VAS), the unweighted score for a respondent's health state (Level Sum Score, LSS) and the Russian health preferences-based weighted score (EQ index). In order to estimate the EQ-5D-5L index, we used a newly developed Russian EQ-5D-3L value set, together with EuroQol Group cross-over methodology. A total of 1020 respondents (18-93 years old) from the general Moscow adult population completed the EQ-5D-5L questionnaire. HRQoL domains with the largest number of identified health limitations were pain/discomfort (48.6%) and anxiety/depression (44.1%). Two hundred seventy-nine respondents (27.0%) did not report any health restrictions. The mean EQ VAS and EQ-5D-5L index were 74.1 (SD 17.3) and 0.907 (0.106) respectively. Multivariate analysis showed that female sex, advanced age and lack of access to the Internet had a negative influence on HRQoL, whereas residence in certain districts had a positive impact. The study provides population norms of health-related quality of life in Moscow, measured according to the EQ-5D-5L questionnaire. These reference values can be used to optimise the effectiveness of resource allocation in healthcare.


Efficacy and Safety of Microencapsulated Benzoyl Peroxide Cream, 5%, in Rosacea: Results From Two Phase III, Randomized, Vehicle-Controlled Trials.
A new formulation of benzoyl peroxide (E-BPO cream, 5%) entraps benzoyl peroxide (BPO) in silica microcapsules. This study assesses the efficacy, safety, and tolerability of E-BPO cream, 5%, in rosacea in two Phase III clinical trials. In two 12-week, randomized, double-blind, vehicle cream-controlled Phase III trials, 733 subjects at least 18 years old with moderate to severe rosacea were randomized (2:1) to once-daily E-BPO cream, 5%, or vehicle. In Study 1, the proportion of subjects achieving IGA clear/almost clear at Week 12 was 43.5 percent for E-BPO cream, 5%, and 16.1 percent for vehicle. In Study 2, the respective values were 50.1 percent and 25.9 percent. In Study 1, the decrease in lesion count from baseline to Week 12 was -17.4 for E-BPO cream, 5%, versus -9.5 for vehicle. In Study 2, the respective values were -20.3 and -13.3 (all P<0.001). The difference was also significant at Week 2. There were no treatment-related serious adverse events; 1.4 percent of subjects (1.8% E-BPO cream, 5%, 0.4% vehicle) discontinued due to adverse events. Assessed local tolerability was found to be similar among subjects in both E-BPO and vehicle. E-BPO was not compared with unencapsulated BPO. E-BPO is an effective and well tolerated treatment for rosacea. Clinicaltrials.gov Identifiers: NCT03564119, NCT03448939.


A Markov chain approach to reconstruction of long haplotypes.
Haplotypes are important for association based gene mapping, but there are no practical laboratory methods for obtaining them directly from DNA samples. We propose simple Markov models for reconstruction of haplotypes for a given sample of multilocus genotypes. The models are aimed specifically for long marker maps, where linkage disequilibrium between markers may vary and be relatively weak. Such maps are ultimately used in chromosome or genome-wide association studies. Haplotype reconstruction with standard Markov chains is based on linkage disequilibrium (LD) between neighboring markers. Markov chains of higher order can capture LD in a neighborhood of a given size. We introduce a more flexible and robust model, MC-VL, which is based on a Markov chain of variable order. Experimental validation of the Markov chain methods on both a wide range of simulated data and real data shows that they clearly out perform previous methods on genetically long marker maps and are highly competitive with short maps, too. MC-VL performs well across different data sets and settings while avoiding the problem of manually choosing an appropriate order for the Markov chain, and it has low computational complexity.


Preparation of fixed antigenic, non-oncogenic and protective neoplastic cells.
Transplantable spontaneous mammary adenocarcinoma and sarcoma P 1798 cells were incubated with vibrio cholera neuraminidase (VCN), then fixed cells demonstrated ability to exclude trypan blue dye and to immunized animals and produce cytotoxic sera of high titers. The fixed neuramindase-treated tumor cells became non-oncogenic and protected the host against high doses of fresh untreated homologous tumors.


Light-induced hydrolysis and rebinding of nonisomerizable bacteriorhodopsin pigment.
Bacteriorhodopsin (bR) is characterized by a retinal-protein protonated Schiff base covalent bond, which is stable for light absorption. We have revealed a light-induced protonated Schiff base hydrolysis reaction in a 13-cis locked bR pigment (bR5.13; lambda(max) = 550 nm) in which isomerization around the critical C13==C14 double bond is prevented by a rigid ring structure. The photohydrolysis reaction takes place without isomerization around any of the double bonds along the polyene chain and is indicative of protein conformational alterations probably due to light-induced polarization of the retinal chromophore. Two photointermediates are formed during the hydrolysis reaction, H450 (lambda(max) = 450 nm) and H430 (lambda(max) = 430 nm), which are characterized by a 13-cis configuration as analyzed by high-performance liquid chromatography. Upon blue light irradiation after the hydrolysis reaction, these intermediates rebind to the apomembrane to reform bR5.13. Irradiation of the H450 intermediate forms the original pigment, whereas irradiation of H430 at neutral pH results in a red shifted species (P580), which thermally decays back to bR5.13. Electron paramagnetic resonance (EPR) spectroscopy indicates that the cytoplasmic side of bR5.13 resembles the conformation of the N photointermediate of native bR. Furthermore, using osmotically active solutes, we have observed that the hydrolysis rate is dependent on water activity on the cytoplasmic side. Finally, we suggest that the hydrolysis reaction proceeds via the reversed pathway of the binding process and allows trapping a new intermediate, which is not accumulated in the binding process.