Proffered Papers 10.30–11.15 Monday 15 September 2003 3 5 year outcome of women with borderline and mild dyskaryosis smears 3 5 year outcome of women with borderline and mild dyskaryosis smears

Aims

• 1 To identify the outcome status of women with borderline and mild dyskaryosis smears.
• 2 To determine whether the presence or absence of koilocytosis influences the outcome status.
• 3 To identify the proportion of women with borderline smears showing koilocytosis.

Materials and methods Borderline and mild dyskaryosis cervical smears diagnosed during January to March 1997 were identified from the laboratory database. Each slide was reviewed by two researchers independently, who then agreed a final consensus diagnosis. All slides were classified according to the presence or absence of koilocytosis. Slides were excluded from the study if the review diagnosis was negative, inadequate or high‐grade dyskaryosis. The outcome status was classified according to the worst lesion identified histologically and/or cytologically during the 5‐year follow‐up period. Results 1974 women were identified with borderline or mild dyskaryosis cervical smears of which 1597 were included in the study. Table 1 shows the outcome status of these women.

Table 1. . The outcome status of these women

Posters. P9 A case of carcinosarcoma presenting in a cervical ThinPrep® sample

Introduction Direct endometrial sampling with cytology and or histology is used at our hospital as part of the investigation of abnormal uterine bleeding. It is used in cases where there is a low clinical suspicion of malignancy. The advantage of the technique is that it can be done as an outpatient procedure with minimal patient discomfort. Reports in the literature give mixed results. We present a 3‐year retrospective of our experience with follow‐up.

Comparison of the Efficacy of the Two Tetracycline‐Containing Sequential Therapy Regimens for the Eradication of Helicobacter Pylori: 5 days Versus 14 days Amoxicillin

Aim: To compare the efficacy of 14‐day and 5‐day amoxicillin treatment on the eradication rate during tetracycline containing sequential H. pylori therapy, and also to compare the eradication rate of this regimen with those used in similar studies performed in Turkey. Method: This study included 112 patients infected with H. pylori that were randomized into 2 groups. In group A, patients (n = 56) received pantoprazole (40 mg BID) and amoxicillin (1 g BID) for 5 days, followed by pantoprazole (40 mg BID), tetracycline (500 mg QID), and metronidazole (500 mg TID) for the remaining 9 days. In group B, patients (n = 56) received pantoprazole (40 mg BID) and amoxicillin (1 g BID) for 5 days, followed by pantoprazole (40 mg BID), tetracycline (500 mg QID), metronidazole (500 mg TID), and amoxicillin (1 g BID) for the remaining 9 days. Eradication rates were calculated using both intention‐to‐treat (ITT) and per‐protocol (PP) analyses. Results: In all, 112 patients were subjected to ITT analysis and 109 patients completed the study. In group A, H. pylori eradication was achieved in 46 (82.1%) of the 56 patients included in the ITT analysis and in 46 (83.6%) of the 55 patients included in the PP analysis. In group B, H. pylori eradication was achieved in 44 (78.57%) of the 56 patients included in the ITT analysis and in 44 (81.48%) of the 54 patients included in the PP analysis ( Table 2 ). The eradication rates were not statistically significant between the 2 groups (p > .005).

Table 2. Eradication rates in the two study groups

P‐1DIRECT‐TO‐VIAL USE OF THE LIQUI‐PREP™ CYTOLOGY SYSTEM

Introduction: The authors initiated the use of Liqui‐PREP? (LGM International Inc., Fort Lauderdale, FL, USA) in August, 2005. Cytotechnologists received extensive (one month) training by cytopathologists experienced in Liquid‐based cytology. The Liqui‐PREP? direct‐to‐vial procedure (LP) was compared to the conventional Pap smears in a routine screening population. Methods: Data derived from 26 178 LP cervical‐vaginal (CV) specimens were compared to data derived from 218 548 conventional Pap smears (CS). Both data sets reflect patient samples collected concurrently (August–December, 2005) by 117 participating outpatient medical practices from a well‐defined geographic area. There were no significant personnel changes during the study period. The diagnostic results, classified according to Bethesda criteria were calculated. Results:

Endoplasmic Reticulum Targeting and Insertion of Tail-Anchored Membrane Proteins by the GET Pathway

Hundreds of eukaryotic membrane proteins are anchored to membranes by a single transmembrane domain at their carboxyl terminus. Many of these tail-anchored (TA) proteins are posttranslationally targeted to the endoplasmic reticulum (ER) membrane for insertion by the guided-entry of TA protein insertion (GET) pathway. In recent years, most of the components of this conserved pathway have been biochemically and structurally characterized. Get3 is the pathway-targeting factor that uses nucleotide-linked conformational changes to mediate the delivery of TA proteins between the GET pretargeting machinery in the cytosol and the transmembrane pathway components in the ER. Here we focus on the mechanism of the yeast GET pathway and make a speculative analogy between its membrane insertion step and the ATPase-driven cycle of ABC transporters.The mechanism of membrane protein insertion into the endoplasmic reticulum (ER) has been extensively studied for many years (Shao and Hegde 2011). From this work, the signal recognition particle (SRP)/Sec61 pathway has emerged as a textbook example of a cotranslational membrane insertion mechanism (Grudnik et al. 2009). The SRP binds a hydrophobic segment (either a cleavable amino-terminal signal sequence or a transmembrane domain) immediately after it emerges from the ribosomal exit tunnel. This results in a translational pause that persists until SRP engages its receptor in the ER and delivers the ribosome-nascent chain complex to the Sec61 channel. Last, the Sec61 channel enables protein translocation into the ER lumen along with partitioning of hydrophobic transmembrane domains into the lipid bilayer through the Sec61 lateral gate (Rapoport 2007).Approximately 5% of all eukaryotic membrane proteins have an ER targeting signal in a single carboxy-terminal transmembrane domain that emerges from the ribosome exit tunnel following completion of protein synthesis and is not recognized by the SRP (Stefanovic and Hegde 2007). Nonetheless, because hydrophobic peptides in the cytoplasm are prone to aggregation and subject to degradation by quality control systems (Hessa et al. 2011), these tail-anchored (TA) proteins still have to be specifically recognized, shielded from the aqueous environment, and guided to the ER membrane for insertion. In the past five years, the guided-entry of TA proteins (GET) pathway has come to prominence as the major machinery for performing these tasks and the enabler of many key cellular processes mediated by TA proteins including vesicle fusion, membrane protein insertion, and apoptosis. This research has rapidly yielded biochemical and structural insights (​and2)2) into many of the GET pathway components (Hegde and Keenan 2011; Chartron et al. 2012a; Denic 2012). In particular, Get3 is an ATPase that uses metabolic energy to bridge recognition of TA proteins by upstream pathway components with TA protein recruitment to the ER for membrane insertion. However, the precise mechanisms of nucleotide-dependent TA protein binding to Get3 and how the GET pathway inserts tail anchors into the membrane are still poorly understood. Here, we provide an overview of the budding yeast GET pathway with emphasis on mechanistic insights that have come from structural studies of its membrane-associated steps and make a speculative juxtaposition with the ABC transporter mechanism.

Table 1.

A catalog of GET pathway component structures

ALGAL RESPONSE TO NUTRIENT ENRICHMENT IN FORESTED OLIGOTROPHIC STREAM1

Nutrient input in streams alters the density and species composition of attached algal communities in open systems. However, in forested streams, the light reaching the streambed (rather than the local nutrient levels) may limit the growth of these communities. A nutrient‐enrichment experiment in a forested oligotrophic stream was performed to test the hypothesis that nutrient addition has only minor effects on the community composition of attached algae and cyanobacteria under light limitation. Moderate nutrient addition consisted of increasing basal phosphorus (P) concentrations 3‐fold and basal nitrogen (N) concentrations 2‐fold. Two upstream control reaches were compared to a downstream reach before and after nutrient addition. Nutrients were added continuously to the downstream reach for 1 year. Algal biofilms growing on ceramic tiles were sampled and identified for more than a year before nutrient addition to 12 months after. Diatoms were the most abundant taxonomic group in the three stream reaches. Nutrient enrichment caused significant variations in the composition of the diatom community. While some taxa showed significant decreases (e.g., Achnanthes minutissima, Gomphonema angustum), increases for other taxa (such as Rhoicosphenia abbreviata and Amphora ovalis) were detected in the enriched reach (for taxonomic authors, see Table 2 ). Epiphytic and adnate taxa of large size were enhanced, particularly during periods of favorable growth conditions (spring). Nutrients also caused a change in the algal chl a, which increased from 0.5–5.8 to 2.1–10.7 μg chl · cm^?2. Our results indicate that in oligotrophic forested streams, long‐term nutrient addition has significant effects on the algal biomass and community composition, which are detectable despite the low light availability caused by the tree canopy. Low light availability moderates but does not detain the long‐term tendency toward a nutrient‐tolerant community. Furthermore, the effects of nutrient addition on the algal community occur in spite of seasonal variations in light, water flow, and water chemical characteristics, which may confound the observations.

Table 2. Percent abundances of the most frequent taxa in three reaches of the Fuirosos stream. U1 and U2 untreated; E, enriched both in the periods before (bef) and after (aft) the enrichment of the E reach. Acronyms identifying the taxa are indicated.

Perioperative Opioid Counseling Reduces Opioid Use Following Primary Total Joint Arthroplasty

BackgroundPreoperative counseling may reduce postoperative opioid requirements; however, there is a paucity of randomized controlled trials (RCTs) demonstrating efficacy. The purpose of this study was to perform an interventional, telehealth-based RCT evaluating the effect of peri-operative counseling on quantity and duration of opioid consumption following primary total joint arthroplasty (TJA).MethodsParticipants were randomized into three groups: 1. Control group, no perioperative counseling; 2. Intervention group, preoperative educational video; 3. Intervention group, preoperative educational video and postoperative acceptance and commitment therapy (ACT). Opioid consumption was evaluated daily for 14 days and at 6 weeks postoperatively. Best-case and worse-case intention to treat analyses were performed to account for non-responses. Bonferroni corrections were applied.Results183 participants were analyzed (63 in Group 1, 55 in Group 2, and 65 in Group 3). At 2 weeks postoperatively, there was no difference in opioid consumption between Groups 1, 2, and 3 (p>0.05 for all). At 6 weeks postoperatively, Groups 2 and 3 had consumed significantly less opioids than Group 1 (p=0.04, p<0.001) (

The relative role of relatives in conspecific brood parasitism

Conspecific brood parasites lay their eggs in the nests of other females in the same population, leading to a fascinating array of possible ‘games’ among parasites and their hosts ( Davies 2000 ; Lyon & Eadie 2008 ). Almost 30 years ago, Andersson & Eriksson (1982) first suggested that perhaps this form of parasitism was not what it seemed—indeed, perhaps it was not parasitism at all! Andersson & Eriksson (1982) observed that conspecific brood parasitism (CBP) was disproportionally common in waterfowl (Anatidae), a group of birds for which natal philopatry is female‐biased rather than the more usual avian pattern of male‐biased natal philopatry. Accordingly, Andersson (1984) reasoned (and demonstrated in an elegantly simple model) that relatedness among females might facilitate the evolution of CBP—prodding us to reconsider it as a kin‐selected and possibly cooperative breeding system rather than a parasitic interaction. The idea was much cited but rarely tested empirically until recently—a number of new studies, empowered with a battery of molecular techniques, have now put Andersson’s hypothesis to the test ( Table 1 ). The results are tantalizing, but also somewhat conflicting. Several studies, focusing on waterfowl, have found clear evidence that hosts and parasites are often related ( Andersson & Åhlund 2000 ; Roy Nielsen et al. 2006 ; Andersson & Waldeck 2007 ; Waldeck et al. 2008 ; Jaatinen et al. 2009 ; Tiedemann et al. 2011 ). However, this is not always the case ( Semel & Sherman 2001 ; Anderholm et al. 2009 ; and see Pöysa 2004 ). In a new study reported in this issue of Molecular Ecology, Jaatinen et al. (2011a) provide yet another twist to this story that might explain not only why such variable results have been obtained, but also suggests that the games between parasites and their hosts—and the role of kinship in these games—may be even more complex than Andersson (1984) imagined. Indeed, the role of kinship in CBP may be very much one of relative degree!

Table 1. A summary of recent studies that have tested for evidence of relatedness between hosts and parasites in avian conspecific brood parasites

Big Data: Astronomical or Genomical?

Genomics is a Big Data science and is going to get much bigger, very soon, but it is not known whether the needs of genomics will exceed other Big Data domains. Projecting to the year 2025, we compared genomics with three other major generators of Big Data: astronomy, YouTube, and Twitter. Our estimates show that genomics is a “four-headed beast”—it is either on par with or the most demanding of the domains analyzed here in terms of data acquisition, storage, distribution, and analysis. We discuss aspects of new technologies that will need to be developed to rise up and meet the computational challenges that genomics poses for the near future. Now is the time for concerted, community-wide planning for the “genomical” challenges of the next decade.We compared genomics with three other major generators of Big Data: astronomy, YouTube, and Twitter. Astronomy has faced the challenges of Big Data for over 20 years and continues with ever-more ambitious studies of the universe. YouTube burst on the scene in 2005 and has sparked extraordinary worldwide interest in creating and sharing huge numbers of videos. Twitter, created in 2006, has become the poster child of the burgeoning movement in computational social science [6], with unprecedented opportunities for new insights by mining the enormous and ever-growing amount of textual data [7]. Particle physics also produces massive quantities of raw data, although the footprint is surprisingly limited since the vast majority of data are discarded soon after acquisition using the processing power that is coupled to the sensors [8]. Consequently, we do not include the domain in full detail here, although that model of rapid filtering and analysis will surely play an increasingly important role in genomics as the field matures.To compare these four disparate domains, we considered the four components that comprise the “life cycle” of a dataset: acquisition, storage, distribution, and analysis ( Data Phase Astronomy Twitter YouTube Genomics Acquisition 25 zetta-bytes/year0.5–15 billion tweets/year500–900 million hours/year1 zetta-bases/year Storage 1 EB/year1–17 PB/year1–2 EB/year2–40 EB/year Analysis In situ data reductionTopic and sentiment miningLimited requirementsHeterogeneous data and analysisReal-time processingMetadata analysisVariant calling, ~2 trillion central processing unit (CPU) hoursMassive volumesAll-pairs genome alignments, ~10,000 trillion CPU hours Distribution Dedicated lines from antennae to server (600 TB/s)Small units of distributionMajor component of modern user’s bandwidth (10 MB/s)Many small (10 MB/s) and fewer massive (10 TB/s) data movementOpen in a separate window     

The Golgin Coiled-Coil Proteins of the Golgi Apparatus

A number of long coiled-coil proteins are present on the Golgi. Often referred to as “golgins,” they are well conserved in evolution and at least five are likely to have been present in the last common ancestor of all eukaryotes. Individual golgins are found in different parts of the Golgi stack, and they are typically anchored to the membrane at their carboxyl termini by a transmembrane domain or by binding a small GTPase. They appear to have roles in membrane traffic and Golgi structure, but their precise function is in most cases unclear. Many have binding sites for Rab family GTPases along their length, and this has led to the suggestion that the golgins act collectively to form a tentacular matrix that surrounds the Golgi to capture Rab-coated membranes in the vicinity of the stack. Such a collective role might explain the lack of cell lethality seen following loss of some of the genes in human familial conditions or mouse models.Coiled-coils are widely occurring protein structural motifs in which two or more α-helices wind around each other to form an extended rod-like structure. Proteins containing such structures are found in many parts of the cell, and play diverse roles including organizing centrosomes, chromatin, and synapses, or serving as molecular motors. As such there may seem little reason to consider them collectively beyond an interest in the structural and biophysical properties of the coiled-coil itself. However, the Golgi is unique amongst the cellular compartments in that several different large coiled-coil proteins are present on its cytoplasmic surface (Gillingham and Munro 2003; Lupashin and Sztul 2005; Short et al. 2005; Ramirez and Lowe 2009). A number of these share a similar organization in that most of the protein is predicted to form a coiled-coil, and that their carboxyl termini mediate attachment to Golgi membranes. They are generally ubiquitously expressed and well conserved in evolution, but their coiled-coil regions are relatively poorly conserved suggesting that much of their length serves as spacer. Given that 500 residues of coiled-coil is ∼75 nm in length then the proteins could extend for ∼100–400 nm. Some of the proteins have regions which appear likely to be unstructured and hence could serve as extensions or hinges to increase the proteins’ reach and flexibility (Oas and Endow 1994; Yamakawa et al. 1996). These shared features suggest that the proteins serve related functions on the Golgi. The term “golgin” is often applied to these proteins having been coined in early studies when several were found as human autoantigens (Fritzler et al. 1993), but the term lacks a clear definition. To provide a focus to this article, I will concentrate on “golgins” as defined by being a protein that is found primarily, if not exclusively, on the Golgi and is predicted to form a homodimeric parallel coiled-coil over most of its length. Proteins with shorter regions of coiled-coil are more likely to have roles distinct to the golgins, especially if further domains are present.Golgin coiled-coil proteins are found on the cis-face of the Golgi, around the rims of the stack and on the trans-face of the Golgi (Fig. 1). The human golgins are summarized in Open in a separate windowFigure 1.The golgin coiled-coil proteins of humans.Schematic representations of known human golgins. Regions predicted to form coiled-coils are shown in gray, and known domains involved in protein function or subcellular targeting are indicated.

Table 1.

The canonical golgins of the human Golgi and their orthologs.

SEAWEED EXTRACTS AS A POTENTIAL TOOL FOR THE ATTENUATION OF OXIDATIVE DAMAGE IN OBESITY‐RELATED PATHOLOGIES1

Recent studies suggest that seaweed extracts are a significant source of bioactive compounds comparable to the dietary phytochemicals such as onion and tea extracts. The exploration of natural antioxidants that attenuate oxidative damage is important for developing strategies to treat obesity‐related pathologies. The objective of this study was to screen the effects of seaweed extracts of 49 species on adipocyte differentiation and reactive oxygen species (ROS) production during the adipogenesis in 3T3‐L1 adipocytes, and to investigate their total phenol contents and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activities. Our results show that high total phenol contents were observed in the extracts of Ecklonia cava (see Table 1 for taxonomic authors) (681.1 ± 16.0 μg gallic acid equivalents [GAE] · g^?1), Dictyopteris undulata (641.3 ± 70.7 μg GAE · g^?1), and Laurencia intermedia (560.9 ± 48.1 μg GAE · g^?1). In addition, DPPH radical scavenging activities were markedly higher in Sargassum macrocarpum (60.2%), Polysiphonia morrowii (55.0%), and Ishige okamurae (52.9%) than those of other seaweed extracts (P < 0.05). Moreover, treatment with several seaweed extracts including D. undulata, Sargassum micracanthum, Chondrus ocellatus, Gelidium amansii, Gracilaria verrucosa, and Grateloupia lanceolata significantly inhibited adipocyte differentiation and ROS production during differentiation of 3T3‐L1 preadipocytes. Furthermore, the production of ROS was positively correlated with lipid accumulation (R² = 0.8149). According to these preliminary results, some of the seaweed extracts can inhibit ROS generation, which may protect against oxidative stress that is linked to obesity. Further studies are required to determine the molecular mechanism between the verified seaweeds and ROS, and the resulting effects on obesity.

Table 1. List of Korean seaweed extracts of 49 species evaluated in this experiment.

A Two-Pathway Analysis of Meiotic Crossing Over and Gene Conversion in Saccharomyces cerevisiae

Several apparently paradoxical observations regarding meiotic crossing over and gene conversion are readily resolved in a framework that recognizes the existence of two recombination pathways that differ in mismatch repair, structures of intermediates, crossover interference, and the generation of noncrossovers. One manifestation of these differences is that simultaneous gene conversion on both sides of a recombination-initiating DNA double-strand break (“two-sidedness”) characterizes only one of the two pathways and is promoted by mismatch repair. Data from previous work are analyzed quantitatively within this framework, and a molecular model for meiotic double-strand break repair based on the concept of sliding D-loops is offered as an efficient scheme for visualizing the salient results from studies of crossing over and gene conversion, the molecular structures of recombination intermediates, and the biochemical competencies of the proteins involved.EUKARYOTES transit from the diplophase to the haplophase via meiosis, which is associated with a number of interrelated processes, including crossing over and gene conversion. These processes involve meiosis-specific, programmed DNA double-strand breaks (DSBs) and their repair (DSBr). DSBr, in turn, is associated with mismatched base pairs and their rectification, referred to as “mismatch repair” or MMR (Bishop et al. 1987). Current efforts to accommodate both the genetic and molecular phenomena associated with meiotic DSBr in yeast (Saccharomyces cerevisiae) have been thoroughly reviewed (e.g., Hollingsworth and Brill 2004; Hoffmann and Borts 2004; Surtees et al. 2004; Hunter 2007; Berchowitz and Copenhaver 2010), but none of the reviews commits to an overall picture with quantitative predictions. This work aims to remedy that lack. Specifically, we have made use of salient published studies to develop, step-by-step, a comprehensive model of meiotic DSBr and MMR. The main features of this model are summarized in FeaturesPairing pathwayDisjunction pathwayProductsCrossovers and noncrossoversCrossovers onlyCrossover InterferenceNo positive interferencePositive interferenceMsh4–Msh5 dependenceNoneTotalBimolecular intermediateLong with junctions not fully ligatedShort with fully ligated Holliday junctionsInvasion heteroduplexPartly ephemeralEphemeralMMR at invasion and annealingDependent on Msh2 and Mlh1NoneMMR near the DSB siteDirected by 3′ invading and annealing endsMlh1 dependent; directed by junction resolutionRole of Msh2 in MMRRecognizes mismatches and attracts Mlh1NoneRole of Msh4–Msh5 in MMRNoneAttracts Mlh1Open in a separate window     

A digital thermocouple thermometer

Measurements of the reproducibility of a random selection of copper/constantan thermocouples were made and it was found that they agreed within 1 ° C. Based on this finding, a digital thermocouple thermometer was designed and constructed incorporating a thermocouple linearizer and cold junction compensation. The instrument

Accuracy of the Completed Digital Thermometer

     

18.

Diminished Susceptibility to Cefoperazone/Sulbactam and Piperacillin/Tazobactam in Enterobacteriaceae Due to Narrow-Spectrum β-Lactamases as Well as Omp Mutation     

Fengzhen Yang  Qi Zhao  Lipeng Wang  Jinying Wu  Lihua Jiang  Li Sheng  Leyan Zhang  Zhaoping Xue  Maoli Yi 《Polish journal of microbiology》2022,71(2):251

Cefoperazone/sulbactam (CSL) and piperacillin/tazobactam (TZP) are commonly used in clinical practice in China because of their excellent antimicrobial activity. CSL and TZP-nonsusceptible Enterobacteriaceae are typically resistant to extended-spectrum cephalosporins such as ceftriaxone (CRO). However, 11 nonrepetitive Enterobacteriaceae strains, which were resistant to CSL and TZP yet susceptible to CRO, were collected from January to December 2020. Antibiotic susceptibility tests and whole-genome sequencing were conducted to elucidate the mechanism for this rare phenotype. Antibiotic susceptibility tests showed that all isolates were amoxicillin/clavulanic-acid resistant and sensitive to ceftazidime, cefepime, cefepime/tazobactam, cefepime/zidebactam, ceftazidime/avibactam, and ceftolozane/tazobactam. Whole-genome sequencing revealed three of seven Klebsiella pneumoniae strains harbored bla_SHV-1 only, and four harbored bla_SHV-1 and bla_TEM-1B. Two Escherichia coli strains carried bla_TEM-1B only, while two Klebsiella oxytoca isolates harbored bla_OXY-1-3 and bla_OXY-1-1, respectively. No mutation in the β-lactamase gene and promoter sequence was found. Outer membrane protein (Omp) gene detection revealed that numerous missense mutations of OmpK36 and OmpK37 were found in all strains of K. pneumoniae. Numerous missense mutations of OmpK36 and OmpK35 and OmpK37 deficiency were found in one K. oxytoca strain, and no OmpK gene was found in the other. No Omp mutations were found in E. coli isolates. These results indicated that narrow spectrum β-lactamases, TEM-1, SHV-1, and OXY-1, alone or in combination with Omp mutation, contributed to the resistance to CSL and TZP in CRO-susceptible Enterobacteriaceae.Antibiotic susceptibility tests

Temperature	Indicated	Error
(°C)	temperature	(°C)
	(°C)
?1.95.75	?195	0.75
?77.02	?78	0.38
0	0	0
52.49	53	0.51
Mean		0.413

Antibiotics	Breakpoint, (μg/ml)	Klebsiella pneumoniae							Escherichia cou		Klebriehd axyoca
		E1	E3	E4	E7	E9	E10	E11	E6	E8	E2	E5
CRO	≤1≥4	≤0.5	≤0.5	≤0.5	≤0.5 1		≤0.5	1	≤0.5	≤0.5	1	1
CAZ	4 ≥16	1	2	1	4	4	4	4	2	4	1 1
FEP	≤2 216 1	1		0.25	1	2	2	2	0.5	2	1 1
AMC	≤8 ≥32	≥128	≥128	≥128	≥128	≥128	≥128	≥128	≥128	≥128	≥128	≥128
CSL	≤16 ≥64	64	64	64	64	≥128	128	≥128	64	128	128	≥128
TZP	≤16 ≥128	≥256	≥256	≥256	≥256	2256	2256	≥256	≥256	≥256	≥256	≥256
FPT	≤2 ≥16	1	0.5	0.06	0.125	2	1	2	0.25	1	0.125	0.25
FPZ	≤2 216	0.25	0.25	0.06	0.125	0.25	0.25 1		0.125	0.25	0.125	0.125
CZA	≤8 216 1		0.5	0.25	0.25	1	0.25	1	0.5	0.5	0.5	0.25
CZT	≤2 28	2	1	0.5 1		2	2	2 1		1	2	2

Open in a separate windowCROceftriaxone, CAZceftazidime, FEPcefepime, AMC:amoxicillin clavulanic-acid, CSLcefoperazone/sulbactam, TZP:piperadllin/tazobactam, FPT:cefepime tazobactam, FPZ:cefepime/zidebactam, CZA:ceftazidime/avibactam, CZTceftolozane/tazobactam Gene sequencing results

Number	Strain	ST	p-Lactamase gene	Promoter sequence mutation	Omp mutation
El	Kpn	45	blaSHV-1, blaTEM-lB	none	OmpK36, OmpK3 7
E3	Kpn	45	blaSHV-1, blaTEM-lB	none	OmpK36. OmpK3 7
E4	Kpn	2854	blaSHV-1	none	OmpK36, OmpK3 7
E7	Kpn	2358	blaSHV-1 - blaTEM-lB	none	OmpK36, OmpK3 7
E9	Kpn	2358	blaSHV-1. blaTEM-lB	none	OmpK36. OmpK3 7
E10	Kpn 18	9	blaSHV-1	none	OmpK36. OmpK3 7
Ell	Kpn	45	blaSHV-1	none	OmpK36, OmpK3 7
E6	Eco	88	blaTEM-lB	none	none
ES	Eco	409	blaTEM-1B	none	none
E2	Kox	194	blaOXY-1-3	none	OmpK36 mutations. OmpK35 and OmpK 37 deficiency
E5	Kox 11		blaOXY-1-1	none	no OmpK (OmpK3 5, OmpK36 and OmpK37) gene found

Open in a separate window     

Diminished Susceptibility to Cefoperazone/Sulbactam and Piperacillin/Tazobactam in Enterobacteriaceae Due to Narrow-Spectrum β-Lactamases as Well as Omp Mutation

Cefoperazone/sulbactam (CSL) and piperacillin/tazobactam (TZP) are commonly used in clinical practice in China because of their excellent antimicrobial activity. CSL and TZP-nonsusceptible Enterobacteriaceae are typically resistant to extended-spectrum cephalosporins such as ceftriaxone (CRO). However, 11 nonrepetitive Enterobacteriaceae strains, which were resistant to CSL and TZP yet susceptible to CRO, were collected from January to December 2020. Antibiotic susceptibility tests and whole-genome sequencing were conducted to elucidate the mechanism for this rare phenotype. Antibiotic susceptibility tests showed that all isolates were amoxicillin/clavulanic-acid resistant and sensitive to ceftazidime, cefepime, cefepime/tazobactam, cefepime/zidebactam, ceftazidime/avibactam, and ceftolozane/tazobactam. Whole-genome sequencing revealed three of seven Klebsiella pneumoniae strains harbored bla_SHV-1 only, and four harbored bla_SHV-1 and bla_TEM-1B. Two Escherichia coli strains carried bla_TEM-1B only, while two Klebsiella oxytoca isolates harbored bla_OXY-1-3 and bla_OXY-1-1, respectively. No mutation in the β-lactamase gene and promoter sequence was found. Outer membrane protein (Omp) gene detection revealed that numerous missense mutations of OmpK36 and OmpK37 were found in all strains of K. pneumoniae. Numerous missense mutations of OmpK36 and OmpK35 and OmpK37 deficiency were found in one K. oxytoca strain, and no OmpK gene was found in the other. No Omp mutations were found in E. coli isolates. These results indicated that narrow spectrum β-lactamases, TEM-1, SHV-1, and OXY-1, alone or in combination with Omp mutation, contributed to the resistance to CSL and TZP in CRO-susceptible Enterobacteriaceae.Antibiotic susceptibility tests

Use of methotrexate therapy is not associated with decreased prevalence of metabolic syndrome

With great interest, we read the article by Toms and colleagues [1] in the previous issue of Arthritis Research & Therapy, in which they assessed prevalences of metabolic syndrome (MetS) in rheumatoid arthritis (RA) patients. Moreover, they identified demographic and clinical factors that may be associated with MetS. Toms and colleagues found prevalences of up to 45% of MetS and demonstrated older age and health status (health assessment questionnaire) to be associated with MetS irrespectively of the definition used. Of most interest, an association between methotrexate (MTX) use and decreased presence of MetS was observed in patients more than 60 years of age. The investigators hypothesized that this may be attributed to a drug-specific effect (and not to an anti-inflammatory effect) either by changing levels of adenosine, which is known to interact with glucose and lipid metabolism, or by an indirect effect mediated through concomitant folic acid administration, thereby decreasing homocysteine levels.Recently, we also examined the prevalence of MetS in (a subgroup of) RA patients in the CARRÉ investigation, a prospective cohort study on prevalent and incident cardiovascular disease and its underlying cardiovascular risk factors [2]. The findings of Toms and colleagues stimulated us to perform additional analyses in our total study population (n = 353).The prevalences of MetS were 35% and 25% (Table ​(Table1)1) according to criteria of National Cholesterol Education Program (NCEP) 2004 and NCEP 2001, respectively. In multivariate backward regression analyses, we found significant associations between body mass index, pulse rate, creatinine levels, hypothyroidism and diabetes mellitus and the presence of MetS independently of the criteria used (Table ​(Table2).2). However, an independent association between single use of MTX or use of MTX in combination with other disease-modifying antirheumatic drugs, on the one hand, and a decreased prevalence of MetS, on the other hand, could not be demonstrated (even in the subgroup of patients over the age of 60).

Table 1

Characteristics of the study population

A special issue of Biophysical Reviews dedicated to the 20th IUPAB (virtual) Congress “in” Foz do Iguaçu

The 20th IUPAB Congress took place online, together with the annual meetings of the Brazilian Biophysical Society and the Brazilian Society for Biochemistry and Molecular Biology, from the 4th to the 8th of October, 2021. The ten keynote lectures, 24 symposia, two poster sessions, and a series of technical seminars covered the full diversity of current biophysical research and its interfaces with other fields. The event had over 1000 attendees, with an excellent gender balance. Although the Americas dominated, there were also significant numbers of participants from Europe, Asia, and Africa.

The International Union of Pure and Applied Biophysics (IUPAB) came into existence in Stockholm in 1961 and has been a member of the International Science Council since 1966 (Solomon 1968). Its overall objectives aim to foster international collaboration in all aspects of biophysics and related areas and to catalyze the advancement of basic biophysical research as well as its many applications. Although IUPAB is active on many fronts, undeniably one of its showcase events is the IUPAB Congress, traditionally organized every three years in different locations worldwide. In 2021, the event was organized and run from Brazil, albeit for the very first time in a virtual format due to travel restrictions imposed by the COVID-19 pandemic. On this occasion, the Congress was organized in conjunction with the annual meetings of both the Brazilian Biophysical Society (SBBf, in its 45th edition) and the Brazilian Society for Biochemistry and Molecular Biology (SBBq, in its 50th edition). Even with the united forces of these well-established local societies, it turned out to be a bumpy ride to bring the event to fruition.Plans for the 20th Congress began in 2016, almost immediately after the decision to hold the event in Brazil, a cause championed by the then-president of the Brazilian Biophysical Society, Marcelo Morales. The original plans had the meeting to be held in the Cidade Maravilhosa (The Wonderful City) of Rio de Janeiro in October 2020. However, it soon became apparent that the political and economic difficulties that the State of Rio was facing at the time meant that it would be wise to search for an alternative venue. The previous experience of SBBq in organizing similar events in the city of Foz do Iguaçu, on the borders with Argentina and Paraguay, made this an obvious choice. Furthermore, the natural attraction of the spectacular Iguaçu waterfalls seemed to be an ideal compensation for Sugar Loaf Mountain, Copacabana beach, and the statue of Christ the Redeemer on Corcovado Mountain.Then came the pandemic. By mid-2020, it had become apparent that there were too many unknowns to make it possible to proceed with an in-person event in October of that year. It was decided to postpone the congress to 2021 but with a firm belief that things would be “back to normal.” Sweet delusion! As 2020 turned into 2021 and the severity and longevity of the pandemic became clearer and clearer (not to mention the abysmal performance of the Brazilian government in failing to rise to the challenge), the inevitable decision was taken to transform the event into an “on-line” congress. This was a first for both the local organizers and the IUPAB.The move to an online format immediately had an impact on the organization of the Young Scientist Program. This was initially envisaged to be a combination of formal and informal activities aimed at uniting about 40 early carrier scientists and post-docs for a couple of days prior to the main event in a stimulating atmosphere conducive to networking. Skillfully conceived, organized, and executed by Eneida de Paula (Campinas) and Eduardo Reis (São Paulo), this too had to be adapted to a “virtual reality.” The successful solution turned out to be a series of fortnightly thematic webinars, including a talk from a recognized authority in the field followed by three or four short presentations from the participants themselves (Table ​(Table1).1). The standard was extremely high and the YSP ended up being a highly effective warm-up to the congress itself. Furthermore, there was excellent geographical diversity among the participants with Europe, Africa, Asia, the Middle East, and both North and South America represented.Table 1Young Scientist Webinar Program