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Wake-up receivers have been proposed to provide continuous sensing in a wide variety of Internet of Things applications. To achieve impedance transformation and passive amplification between the antenna and rectifier node, current wake-up receivers employ large magnetic transformers that exhibit both low Q and inductance per unit area in planar CMOS technology. The adoption of piezoelectric MEMS resonators to replace magnetic transformers offers an area-efficient, high-Q, monolithic solution that allows large voltage amplification for ultra-low-power applications. AlN Contour Mode Resonators (CMRs) are an emerging class of piezoelectric MEMS that offers frequency reconfiguration via lithography.

A new wake-up receiver (WuRx) designed in 0.13 μm CMOS process is hybrid-integrated with a micro-electromechanical system (MEMS) RF resonator. While only consuming 166 nW of power (18.8 nW for the comparator and 147 nW for periphery), the WuRx is capable of detecting RF signals as weak as -60 dBm. In order to achieve this sensitivity, a passive voltage-boosting network comprised of a high quality factor (high-Q) piezoelectric MEMS resonator is utilized, in place of an inductor, to amplify the received voltages applied to a CMOS rectifier. The output of the rectifier is then applied to a low-power comparator used to set a logical bit that indicates when an RF signal has been detected. The trade-offs in designing the voltage boosting network are explained and an equation for the optimum number of rectifier stages is derived.

Background: Coronary artery disease (CAD) is a common finding in patients undergoing transcatheter aortic valve implantation (TAVI). However, its prognostic significance and its management remains controversial., Aims: This study sought to determine whether the presence of CAD, its complexity, and angiography-guided percutaneous coronary intervention (PCI) are associated with outcomes after TAVI., Methods: All patients undergoing TAVI at a tertiary referral center between 2008 and 2018 were included in a prospective observational study. Baseline SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score (SS) and a residual SS after PCI were calculated. The endpoints on the 5 year follow-up were all-cause mortality and a composite of mayor cardiovascular adverse events (MACE)., Results: In 379 patients, the presence of CAD and its complexity were not significantly associated with worse 5-year survival after TAVI, with a mortality for SS0 of 45%; for SS 1-22 of 36.5% (HR 0.77; 95% CI 0.53-1.11, p = 0.15) and for SS > 22 of 42.1% (HR 1.24; 95% CI 0.59-2.63, p = 0.57). Regarding the combined event of MACE, there were also no statistically significant differences between patients with CAD and without CAD (56.8% in patients without CAD and 54.9% in patients with CAD; HR 1.06; 95% CI 0.79-1.43, p = 0.7). Angiography-guided PCI or completeness of revascularization was not associated with different outcomes., Conclusions: In the present analysis, neither the presence nor the extent of CAD, nor the degree of revascularization, was associated with a prognostic impact in patients undergoing TAVI at 5-year follow-up., (© 2023 Wiley Periodicals LLC.)

Background: The health risks faced by older adults are diverse; however, little has been explored about the use and abuse of psychoactive substances in this population. The seclusion imposed by the situation that prevails due to SARS-CoV-2 has increased the feelings of loneliness, isolation and sadness associated with this age, which makes them a risk factor for drug use., Objective: To analyze the consumption of legal and illegal drugs in people over 60 years of age who are Facebook users and its relationship with symptoms of depression during the SARS-CoV-2 pandemic., Material and Methods: Study carried out on 380 elderly people, Facebook users, who answered a questionnaire published online, which inquired about: sociodemographic data, frequency and amount of legal and illegal drug use, and depressive symptomatology., Results: 50.26% were women; the average age was 66.79 years (SD=5.81); 31.05% consumed alcohol in the last 30 days, 22.63% tobacco, tranquilizers without medical prescription 16.05% and marijuana 7.89%. The consumption of other illegal drugs did not exceed 2.6% of the population. When comparing between users and non-users, it turned out that consumption in the last 30 days was slightly higher in women, in single people and no differences were observed depending on the level of schooling. Mild and severe depressive symptoms were found to be associated with all drugs except tobacco and opiates., Discussion and Conclusions: The results obtained demonstrate the need to make drug use visible among older adults and to develop strategies that reduce the mood disorders they may be experiencing, such as fear, anguish and depression. When comparing between users and non-users, it turned out that consumption in the last 30 days was slightly higher in women, in single people and no differences were observed depending on the level of schooling., (Copyright © 2022 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Polymicrobial infections are more challenging to treat and are recognized as responsible for significant morbidity and mortality. It has been demonstrated that multiple Gram-negative organisms take advantage of the effects of Staphylococcus aureus α-toxin on mucosal host defense, resulting in proliferation and dissemination of the co-infecting pathogens. Through phenotypic approaches, we observed a decrease in the motility of A. baumannii A118 after exposure to cell-free conditioned media (CFCM) of S. aureus strains, USA300 and LS1. However, the motility of A. baumannii A118 was increased after exposure to the CFCM of S. aureus strains USA300 Δ hla and S. aureus LSI Δ agrA . Hemolytic activity was seen in A118, in the presence of CFCM of S. aureus LS1. Further, A. baumannii A118 showed an increase in biofilm formation and antibiotic resistance to tetracycline, in the presence of CFCM of S. aureus USA300. Transcriptomic analysis of A. baumannii A118, with the addition of CFCM from S. aureus USA300, was carried out to study A. baumannii response to S. aureus' released molecules. The RNA-seq data analysis showed a total of 463 differentially expressed genes, associated with a wide variety of functions, such as biofilm formation, virulence, and antibiotic susceptibility, among others. The present results showed that A. baumannii can sense and respond to molecules secreted by S. aureus . These findings demonstrate that A. baumannii may perceive and respond to changes in its environment; specifically, when in the presence of CFCM from S. aureus .

Objectives: Acinetobacter baumannii is an opportunistic nosocomial pathogen that is the main focus of attention in clinical settings owing to its intrinsic ability to persist in the hospital environment and its capacity to acquire determinants of resistance and virulence. Here we present the genomic sequencing, molecular characterisation and genomic comparison of two A. baumannii strains belonging to two different sequence types (STs), one sporadic and one widely distributed in our region., Methods: Whole-genome sequencing (WGS) of Ab42 and Ab376 was performed using Illumina MiSeq-I and the genomes were assembled with SPAdes. ARG-ANNOT, CARD-RGI, ISfinder, PHAST, PlasmidFinder, plasmidSPAdes and IslandViewer were used to analyse both genomes., Results: Genome analysis revealed that Ab42 belongs to ST172, an uncommon ST, whilst Ab376 belongs to ST25, a widely distributed ST. Molecular characterisation showed the presence of two antibiotic resistance genes in Ab42 and nine in Ab376. No insertion sequences were detected in Ab42, however 22 were detected in Ab376. Moreover, two prophages were found in Ab42 and three in Ab376. In addition, a CRISPR-cas type I-Fb and two plasmids, one of which harboured an AbGRI1-like island, were found in Ab376., Conclusions: We present WGS analysis of twoA. baumannii strains belonging to two different STs. These findings allowed us to characterise a previously undescribed ST (ST172) and provide new insights to the widely studied ST25., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the last years, an increasing number of untreatable infections caused by drug-resistant microbes have impacted the health care system. Worldwide, infections caused by carbapenem-resistant (CR) Gram-negative bacilli have dramatically increased. Among the CR-Gram-negative bacilli, those producing carbapenemases, such as NDM-1, are the main concern. Different Enterobacterales harboring NDM-1 have been reported lately. Providencia stuartii, a member of the Morganellaceae family, is ubiquitous in the environment, but is also known to cause nosocomial infections. Here we describe the genomic analysis of two NDM-1- producing P. stuartii strains recovered from the same patient as well as other carbapenem resistant strains recovered from the same hospital. As a result of the genomic analysis thirteen resistance genes, including three to β-lactams (bla OXA-1 , bla TEM-1 , bla NDM-1 ), four to aminoglycosides (aphA6, aac(3)-IId, aac(2')-Ia, aac(6')-Ib-cr5), one to sulfonamides (sul1), two to chloramphenicol (catB3, catA3), one to rifampicin, one to bleomycin (ble), and one to tetracycline (tet(B)) were found. Moreover, a variety of mobile genetic elements, such as insertion sequences, plasmids and phage- related sequences, were found within P. stuartii genomes. The spread of carbapenem-resistant isolates remains a significant clinical and public health concern. Therefore, we considered that the detection of CR isolates is an essential step in addressing this problem.

A 4-year surveillance of carbapenem-resistant Acinetobacter spp. isolates in Argentina identified 40 strains carrying bla NDM-1 Genome sequencing revealed that most were Acinetobacter baumannii , whereas seven represented other Acinetobacter spp. The A. baumannii genomes were closely related, suggesting recent spread. bla NDM-1 was located in the chromosome of A. baumannii strains and on a plasmid in non- A. baumannii strains. A resistance gene island carrying bla PER-7 and other resistance determinants was found on a plasmid in some A. baumannii strains., (Copyright © 2020 American Society for Microbiology.)

Acinetobacter baumannii is a feared, drug-resistant pathogen, characterized by its ability to resist extreme environmental and nutrient-deprived conditions. Previously, we showed that human serum albumin (HSA) can increase foreign DNA acquisition specifically and alter the expression of genes associated with pathogenicity. Moreover, in a recent genome-wide transcriptomic study, we observed that pleural fluid (PF), an HSA-containing fluid, increases DNA acquisition, can modulate cytotoxicity, and control immune responses by eliciting changes in the A. baumannii metabolic profile. In the present work, using more stringent criteria and focusing on the analysis of genes related to pathogenicity and response to stress, we analyzed our previous RNA-seq data and performed phenotypic assays to further explore the impact of PF on A. baumannii's microbial behavior and the strategies used to overcome environmental stress. We observed that PF triggered differential expression of genes associated with motility, efflux pumps, antimicrobial resistance, biofilm formation, two-component systems (TCSs), capsule synthesis, osmotic stress, and DNA-damage response, among other categories. Phenotypic assays of A. baumannii A118 and two other clinical A. baumannii strains, revealed differences in their responses to PF in motility, biofilm formation, antibiotic susceptibility, osmotic stress, and outer membrane vesicle (OMV) production, suggesting that these changes are strain specific. We conclude that A. baumannii's pathoadaptive responses is induced by HSA-containing fluids and must be part of this bacterium armamentarium to persist in hostile environments.

The increasing use of polymyxins as last-resort drugs for managing infections by Acinetobacter baumannii has led to the emergence of resistance. This study aimed to determine the resistance mechanisms in Acinetobacter baumannii isolates with colistin MIC ≥ 4 mg/L and to relate the mechanisms of resistance with the difficulties in detecting them. Absolute agreement among the different methodologies (Phoenix automatized system, broth and agar dilution, and a rapid colorimetric test) in the 140 colistin-susceptible isolates was observed; whereas in the 25 resistant isolates, the performance varied according to the colistin MIC value. Most of the discrepancies (irrespective of the methodology that was used) were observed in isolates with an MIC value close to the breakpoint. The number of errors in each method in the resistant isolates was as follows: rapid test, four of 25 (16%); agar dilution, eight of 25 (32%); Phoenix system, 13 of 25 (52%) and its manual reading at 24 h, eight of 25 (32%). Categorical errors were detected in 13 isolates: slow growth was the main reason in five isolates, whereas in the remaining eight isolates, slow growth was detected together with a low proportion of colistin-resistant subpopulations and the colistin MIC value was close to the breakpoint value. To understand the probable reason for the observed MIC values, sequencing of genes associated with colistin resistance was performed. Mutations at lpxA, lpxC, and pmrB genes were detected and it was observed that isolates carrying mutations in lpxC presented slow growth at killing curves., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Our previous data show that serum albumin can trigger natural transformation in Acinetobacter baumannii. However, extracellular matrix/basal membrane components, norepinephrine, and mucin did not have a significant effect on this process. Therefore, the effect of human products appears to be albumin specific, as both BSA and HSA have been shown to increase of natural transformation.

Acinetobacter baumannii ( Ab ) is one of the most treacherous pathogens among those causing hospital-acquired pneumonia (HAP). A. baumannii possesses an adaptable physiology, seen not only in its antibiotic resistance and virulence phenotypes but also in its metabolic versatility. In this study, we observed that A. baumannii undergoes global transcriptional changes in response to human pleural fluid (PF), a key host-derived environmental signal. Differential gene expression analyses combined with experimental approaches revealed changes in A. baumannii metabolism, affecting cytotoxicity, persistence, bacterial killing, and chemotaxis. Over 1,220 genes representing 55% of the differentially expressed transcriptomic data corresponded to metabolic processes, including the upregulation of glutamate, short chain fatty acid, and styrene metabolism. We observed an upregulation by 1.83- and 2.61-fold of the pyruvate dehydrogenase complex subunits E3 and E2, respectively. We also found that pyruvate (PYR), in conjunction with PF, triggers an A. baumannii pathogenic behavior that adversely impacts human epithelial cell viability. Interestingly, PF also amplified A. baumannii cytotoxicity against murine macrophages, suggesting an immune evasion strategy implemented by A. baumannii . Moreover, we uncovered opposing metabolic strategies dependent on the degree of pathogenicity of the strains, where less pathogenic strains demonstrated greater utilization of PYR to promote persister formation in the presence of PF. Additionally, our transcriptomic analysis and growth studies of A. baumannii suggest the existence of an alternative phenylalanine (PA) catabolic route independent of the phenylacetic acid pathway, which converts PA to phenylpyruvate (PP) and shuttles intermediates into styrene metabolism. This alternative route promoted a neutrophil-evasive state, as PF-induced degradation of PP significantly reduced overall human neutrophil chemotaxis in ex vivo chemotactic assays. Taken together, these data highlight A. baumannii pathoadaptabililty in response to host signals and provide further insight into the role of bacterial metabolism in virulence traits, antibiotic persistence strategies, and host innate immune evasion.

Diabetic foot ulcer infections are frequently polymicrobial in nature and exhibit increased morbidity and mortality, as well as, treatment failures. Interactions between Acinetobacter baumannii and Staphylococcus aureus were studied, which showed strain-dependent changes in growth and antibiotic susceptibility. This study examined the interactions between two clinical strains of A. baumannii (1929) and S. aureus (1928) that were recovered from skin and soft tissues of a diabetic patient. When S. aureus 1928 and A. baumannii 1929 were co-cultured together, there was no significant decrease in growth in either clinical strains, indicating that both strains can co-exist in the same site of infection. Additionally, neither strains experienced statistically significant changes in susceptibility. These findings highlight that these two pathogens can be found in the same niche of infection, which may lead to more aggressive outcome of the infection.

In 2014, a novel species of Acinetobacter , strain A47, determined to be hospital-acquired was recovered from a single patient soft tissue sample following a traumatic accident. The complexity of the Acinetobacter genus has been established, and every year novel species are identified. However, specific features and virulence factors that allow members of this genus to be successful pathogens are not well understood. Utilizing both genomic and phenotypic approaches, we identified distinct features and potential virulence factors of the A47 strain to understand its pathobiology. In silico analyses confirmed the uniqueness of this strain and other comparative and sequence analyses were used to study the evolution of relevant features identified in this isolate. The A47 genome was further analyzed for genes associated with virulence and genes involved in type IV pili (T4P) biogenesis, hemolysis, type VI secretion system (T6SS), and novel antibiotic resistance determinants were identified. A47 exhibited natural transformation with both genomic and plasmid DNA. It was able to form biofilms on different surfaces, to cause hemolysis of sheep and rabbit erythrocytes, and to kill competitor bacteria. Additionally, surface structures with non-uniform length were visualized with scanning electron microscopy and proposed as pili-like structures. Furthermore, the A47 genome revealed the presence of two putative BLUF type photoreceptors, and phenotypic assays confirmed the modulation by light of different virulence traits. Taken together, these results provide insight into the pathobiology of A47, which exhibits multiple virulence factors, natural transformation, and the ability to sense and respond to light, which may contribute to the success of an A47 as a hospital dwelling pathogen.

The human pathogen Acinetobacter baumannii possesses high genetic plasticity and frequently acquires antimicrobial resistance genes. Here we investigated the role of natural transformation in these processes. Genomic DNA from different sources, including from carbapenem-resistant Klebsiella pneumoniae strains, was mixed with A. baumannii A118 cells. Selected transformants were analysed by whole-genome sequencing. In addition, bioinformatics analyses and in silico gene flow prediction were also performed to support the experimental results. Transformant strains included some that became resistant to carbapenems or changed their antimicrobial susceptibility profile. Foreign DNA acquisition was confirmed by whole-genome analysis. The acquired DNA most frequently identified corresponded to mobile genetic elements, antimicrobial resistance genes and operons involved in metabolism. Bioinformatics analyses and in silico gene flow prediction showed continued exchange of genetic material between A. baumannii and K. pneumoniae when they share the same habitat. Natural transformation plays an important role in the plasticity of A. baumannii and concomitantly in the emergence of multidrug-resistant strains., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Burkholderia contaminans is a member of the Burkholderia cepacia complex (Bcc), a pathogen with increasing prevalence among cystic fibrosis (CF) patients and the cause of numerous outbreaks due to the use of contaminated commercial products. The antibiotic resistance determinants, particularly β-lactamases, have been poorly studied in this species. In this work, we explored the whole genome sequence (WGS) of a B. contaminans isolate (FFH 2055) and detected four putative β-lactamase-encoding genes. In general, these genes have more than 93% identity with β-lactamase genes found in other Bcc species. Two β-lactamases, a class A (Pen-like, suggested name PenO) and a class D (OXA-like), were further analyzed and characterized. Amino acid sequence comparison showed that Pen-like has 82% and 67% identity with B. multivorans PenA and B. pseudomallei PenI, respectively, while OXA-like displayed strong homology with class D enzymes within the Bcc, but only 22-44% identity with available structures from the OXA family. PCR reactions designed to study the presence of these two genes revealed a heterogeneous distribution among clinical and industrial B. contaminans isolates. Lastly, bla PenO gene was cloned and expressed into E. coli to investigate the antibiotic resistance profile and confers an extended-spectrum β-lactamase (ESBL) phenotype. These results provide insight into the presence of β-lactamases in B. contaminans, suggesting they play a role in antibiotic resistance of these bacteria.

Transformation is one of the mechanisms of acquisition of foreign genetic material leading to the emergence of multidrug resistant (MDR) bacteria. Recently, human serum albumin (HSA) was shown to specifically increase transformation frequency in the nosocomial pathogen Acinetobacter baumannii. To further assess the relevance of HSA as a possible modulator of A. baumannii transformation in host-pathogen interactions, in this work we examined the effect of different human fluids. We observed a significant increase in transformation frequencies in the presence of pleural fluid, whole blood cells and liquid ascites, and to a lesser extent with urine. The observed effects correlate with both HSA and bacterial content found in the assayed patient fluids. Taken together, these results are in agreement with our previous findings that highlight HSA as a possible host signal with the ability to trigger natural transformation in A. baumannii., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Knockdown of orexin/hypocretin 2 receptor (Orx 2 ) in the basolateral amygdala (BLA) affects anxious and depressive behavior. We use a new behavioral paradigm, the Stress Alternatives Model (SAM), designed to improve translational impact. The SAM induces social stress in adult male mice by aggression from larger mice, allowing for adaptive decision-making regarding escape. In this model, mice remain (Stay) in the oval SAM arena or escape from social aggression (Escape) via routes only large enough for the smaller mouse. We hypothesized intracerebroventricular (icv) stimulation of Orx 2 receptors would be anxiolytic and antidepressive in SAM-related social behavior and the Social Interaction/Preference (SIP) test. Conversely, we predicted that icv antagonism of Orx 2 receptors would promote anxious and depressive behavior in these same tests. Anxious behaviors such as freezing (both cued and conflict) and startle are exhibited more often in Stay compared with Escape phenotype mice. Time spent attentive to the escape route is more frequent in Escape mice. In Stay mice, stimulation of Orx 2 receptors reduces fear conditioning, conflict freezing and startle, and promotes greater attention to the escape hole. This anxiolysis was accompanied by activation of a cluster of inhibitory neurons in the amygdala. A small percentage of those Stay mice also begin escaping; whereas Escape is reversed by the Orx 2 antagonist. Escape mice were also Resilient, and Stay mice Susceptible to stress (SIP), with both conditions reversed by Orx 2 antagonism or stimulation respectively. Together, these results suggest that the Orx 2 receptor may be a useful potential target for anxiolytic or antidepressive therapeutics., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acinetobacter baumannii is a multidrug resistant nosocomial pathogen that shows an outstanding ability to undergo genetic exchange, thereby acquiring different traits that contribute to its success. In this work, we identified genetic features of an indigo-pigmented A. baumannii strain (Ab33405) that belongs to the clonal complex CC113 B /CC79 P . Ab33405 possesses a high number of genes coding for antibiotic resistance and virulence factors that may contribute to its survival, not only in the human host, but also in the hospital environment. Thirteen genes conferring resistance to different antibiotic families (trimethoprim, florfenicol, β-lactams, aminoglycosides and sulfonamide) as well as the adeIJK genes and the capsule locus (KL) and outer core locus (OCL) were identified. Ab33405 includes 250 unique genes and a significant number of elements associated with Horizontal Gene Transfer, such as insertion sequences and transposons, genomic islands and prophage sequences. Also, the indigo-pigmented uncommon phenotype that could be associated with the monooxygenase or dioxygenase enzyme coded for by the iacA gene within the iac cluster was probably conferred by insertion of a 18-kb DNA fragment into the iacG gene belonging to this cluster. The Ab33405 genome includes all type VI secretion system genes and killing assays showed the ability of Ab33045 to kill Escherichia coli. In addition, Ab33405 can modulate susceptibility antibiotics when exposed to blue light.

In the past few decades Acinetobacter baumannii has emerged as a notorious nosocomial pathogen because of its ability to acquire genetic material and persist in extreme environments. Recently, human serum albumin (HSA) was shown to significantly increase natural transformation frequency in A. baumannii. This observation led us to perform transcriptomic analysis of strain A118 under HSA induction to identify genes that are altered by HSA. Our results revealed the statistically significant differential expression of 296 protein-coding genes, including those associated with motility, biofilm formation, metabolism, efflux pumps, capsule synthesis, and transcriptional regulation. Phenotypic analysis of these traits showed an increase in surface-associated motility, a decrease in biofilm formation, reduced activity of a citric acid cycle associated enzyme, and increased survival associated with zinc availability. Furthermore, the expression of genes known to play a role in pathogenicity and antibiotic resistance were altered. These genes included those associated with RND-type efflux pumps, the type VI secretion system, iron acquisition/metabolism, and ß-lactam resistance. Together, these results illustrate how human products, in particular HSA, may play a significant role in both survival and persistence of A. baumannii.

Ochrobactrum anthropi, a rare human pathogen, has been isolated predominantly from patients with catheter-related bacteraemia and rarely from other infections. In 2016, six cases of pseudo-bacteraemia caused by carbapenem-resistant O. anthropi isolates were recovered from an Argentinian hospital. The resistant phenotype exposed by the isolates caught our attention and led to an extensive epidemiologic investigation. Here we describe the characterization of a carbapenem-resistant O. anthropi outbreak whose probable cause was by contaminated collection tubes. The genome analysis of one strain revealed the presence of various resistant determinants. Among them, a metal-dependent hydrolase of the β-lactamase superfamily I, phnP, was found. Lately the recovery of unusual multidrug-resistant pathogens in the clinical setting has increased, thus emphasizing the need to implement standardized infection control practice and epidemiologic investigation to identify the real cause of hospital outbreaks.

Carbapenem-resistant Enterobacteriaceae is a growing concern worldwide. Klebsiella pneumoniae is an important nosocomial pathogen with a high capacity for nosocomial spread. We described the occurrence of plasmid-encoded KPC-2-harbouring K. pneumoniae isolates recovered from a neurosurgical centre in Argentina. The bla KPC-2 gene was surrounded by IS kpn6 and IS kpn7 .

This chapter details the ways youth community organizing strategies can inform leadership educators' approaches to engaging marginalized youth in leadership development for social change., (© 2015 Wiley Periodicals, Inc., A Wiley Company.)

Purpose: To assess the risk of damage to the popliteal neurovascular structures when inserting the needle through the posterior aspect of the knee during inside-out suture of the posterior horn of the medial meniscus., Methods: The first stage of our study consisted of simulating a virtual meniscal suture during magnetic resonance imaging by tracing a line from 3 different points (located medially [MP], centrally [CP], and laterally [LP] to the patellar tendon) to the posterior horn of the medial meniscus. This procedure was undertaken both at rest and with valgus stress. The next phase involved the suture of the posterior horns of medial menisci taken from cadaveric specimens, the needle being inserted through 3 separate locations (again located medially [MP], centrally [CP], and laterally [LP] to the patellar tendon). Finally, the distance from each suture thread to the aforementioned neurovascular bundle was measured., Results: During the magnetic resonance imaging study, the measured distances at rest were 26.4 mm for MP, 28.8 mm for CP, and 31 mm for LP, whereas those recorded with valgus stress were 21.7 mm for MP, 23.6 mm for CP, and 26 mm for LP. In the second phase of the study (cadaveric specimen suture), the distances obtained were 22.6 mm for MP, 27.6 mm for CP, and 33 mm for LP., Conclusions: Our results indicate that when the needle is inserted through the 3 points investigated into the posteromedial region of the knee (10 mm from the posterior horn of the internal meniscus) during inside-out suture, it is far enough from the popliteal neurovascular bundle for the maneuver to be performed with a reasonable safety margin. However, this margin can be increased further still if the needle is inserted into the joint through a point located laterally to the patellar tendon., Clinical Relevance: Inside-out suture performed 10 mm from the posterior horn of the internal meniscus through the portals studied offers a sufficient margin of safety to avoid damage to the popliteal neurovascular bundle., (Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Breast cancer (BC) remains the cancer with highest mortality among women in the United States. Entry of BC cells (BCCs) in bone marrow (BM) leads to poor prognosis. This review discusses studies showing interactions between BCCs and BM stroma, consequently providing BCCs with advantages of survival within BM. Myc transcription factor is investigated as a link between the transforming properties of peptides derived from the preprotachykinin-I gene (PPT-I) and Neurokinin-1 (NK1) receptor. A co-culture method previously described to model early integration of BCC in BM is used to study timeline changes of PPT-I and TGF-beta using northern analyses and a bioassay, respectively. The results show changes of both genes in BCCs and BM stroma. Relevance of these changes to homeostasis in BM is discussed. Myc has been shown to link the expressions of TGF-beta1 and PPT-I in BCCs. We now show a role for Myc in the expression of NK1. PPT-I and the chemokine SDF-1alpha induce the expression of each other through an autocrine mechanism. Since a role for Myc in SDF-1alpha-PPT-I axis has not been studied, we speculate on this finding, based on the cell-homing property of SDF-1alpha. Since Myc could be oncogenic, it might be involved in the transforming properties of PPT-I and NK1 while SDF-1alpha could be involved in cell-homing of BCCs through the regulation of PPT-I. The findings are discussed in the context of other related reports.

Management issues in acute coronary syndromes (ACSs) with regard to patients with renal insufficiency or failure are complex. Renal patients have a greater risk for bleeding compared with those with normal renal function because of prolonged bleeding time and platelet dysfunction. Some of the drugs used have significant renal excretion, such as the glycoprotein IIb/IIIa receptor antagonists. Additionally, thrombolytics are underused, which contributes to the delay in instituting immediate treatment of acute myocardial infarction. Clinical data regarding the optimum management of ACSs in renal patients are still lacking. In this article, we review the available data on the use of antithrombotic agents, particularly in patients with renal impairment.

The differential diagnosis of tumors at the base of the skull comprises meningiomas, neurinomas, gliomas, metastatic carcinomas, chordomas, epidermoids, and pituitary adenomas. About half of the pituitary adenomas are prolactinomas which are unique in a sense that medical therapy causes rapid tumor shrinkage and symptomatic improvement. We report on two patients in which the diagnosis of an invasive macroprolactinoma was masked by apparently low prolactin levels caused by a high-dose hook effect in the chemiluminometric assay. The first case a 49 year old male with impairment of hearing on the left side was presented in the Department of Otorhinolaryngology. A massive invasively growing tumor was demonstrated on a cranial MRI. Endocrine tests revealed normal pituitary function and normoprolactinemia. The patient underwent debulking surgery, occipitocervical fusion because of destruction of the first cervical vertebra and subsequent irradiation. The histopathological diagnosis was invasive prolactinoma. A repeat prolactin (PRL) sample, which was assayed using serial dilutions, revealed a real PRL level of 89,700 ng/ml. Dopamine agonist therapy was initiated under which PRL levels declined in parallel with tumor size. The second case a 40 year old male was presented with acute visual loss. Cranial MRI showed a large tumor at the base of the skull. Based on a transnasal biopsy, the preliminary diagnosis was a poorly differentiated carcinoma for which emergency irradiation was performed. Endocrine tests demonstrated partial hypopituitarism and moderate hyperprolactinemia. Hydrocortisone was substituted and dopamine agonist therapy was started because of moderate hyperprolactinemia. The final histopathological diagnosis was invasive prolactinoma. A repeat PRL sample assayed in serial dilution demonstrated an apparent rise in PRL with a maximum value of 6,460 ng/ml. Under dopamine agonist therapy, PRL declined to normal values, tumor size decreased and cranial nerve palsies disappeared. The apparently falsely low prolactin levels in the initial work-up of both patients were caused by a high-dose hook effect in the PRL assay. Serial dilutions of serum PRL samples is, therefore, mandatory in the diagnostic work-up of patients with large invasive tumors at the base of the skull. This avoids unnecessary aggressive and dangerous treatment like surgery or radiotherapy in cases where pharmacological treatment may be the choice.

Despite the high incidence of coronary artery disease in patients with renal impairment, its diagnosis and management remains difficult. The treatment of acute coronary syndrome in this particular group of patients is more complex than in patients with normal renal function. They have a high prevalence of asymptomatic cardiac ischemia. Abnormal baseline electrocardiogram (ECG) findings and nonspecific elevation of cardiac enzymes may be present. Studies are lacking regarding their management mainly because they have been excluded or were not studied as a subgroup in the clinical trials. Thrombolytics are underused during acute myocardial infarction. Heparin, mainly low-molecular weight heparin, for unstable angina and non-Q wave myocardial infarction, should be used with caution because the higher risk for bleeding. Other medications, such as aspirin, metoprolol, and nitroglycerin should be used as in the general population. The newer platelet glycoprotein IIb/IIIa inhibitors may need renal dose adjustment. Revascularization should be pursued if necessary by percutaneous coronary intervention or coronary artery bypass grafting. However, the prognosis and risk of revascularization versus medical therapy have not been determined yet.