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1.
Annu Rev Neurosci ; 39: 41-56, 2016 07 08.
Article in English | MEDLINE | ID: mdl-27050321

ABSTRACT

Many exciting studies have begun to elucidate the genetics of the morphological and physiological diversity of ants, but as yet few studies have investigated the genetics of ant behavior directly. Ant genomes are marked by extreme rates of gene turnover, especially in gene families related to olfactory communication, such as the synthesis of cuticular hydrocarbons and the perception of environmental semiochemicals. Transcriptomic and epigenetic differences are apparent between reproductive and sterile females, males and females, and workers that differ in body size. Quantitative genetic approaches suggest heritability of task performance, and population genetic studies indicate a genetic association with reproductive status in some species. Gene expression is associated with behavior including foraging, response to queens attempting to join a colony, circadian patterns of task performance, and age-related changes of task. Ant behavioral genetics needs further investigation of the feedback between individual-level physiological changes and socially mediated responses to environmental conditions.


Subject(s)
Ants/genetics , Behavior, Animal/physiology , Gene Expression/physiology , Reproduction/physiology , Social Behavior , Animals , Environment , Humans
2.
Horm Behav ; 122: 104757, 2020 06.
Article in English | MEDLINE | ID: mdl-32305342

ABSTRACT

The traditional focus of physiological and functional genomic research is on molecular processes that play out within a single multicellular organism. In the colonial (eusocial) insects such as ants, bees, and termites, molecular and behavioral responses of interacting nestmates are tightly linked, and key physiological processes are regulated at the scale of the colony. Such colony-level physiological processes regulate nestmate physiology in a distributed fashion, through various social communication mechanisms. As a result of physiological decentralization over evolutionary time, organismal mechanisms, for example related to pheromone detection, hormone signaling, and neural signaling pathways, are deployed in novel contexts to influence nestmate and colony traits. Here we explore how functional genomic, physiological, and behavioral studies can benefit from considering the traits of eusocial insects in this light. We highlight functional genomic work exploring how nestmate-level and colony-level traits arise and are influenced by interactions among physiologically-specialized nestmates of various developmental stages. We also consider similarities and differences between nestmate-level (organismal) and colony-level (superorganismal) physiological processes, and make specific hypotheses regarding the physiology of eusocial taxa. Integrating theoretical models of distributed systems with empirical functional genomics approaches will be useful in addressing fundamental questions related to the evolution of eusociality and collective behavior in natural systems.


Subject(s)
Behavior, Animal/physiology , Genome, Insect/physiology , Insecta/genetics , Insecta/physiology , Social Behavior , Animals , Ants/genetics , Ants/physiology , Bees/genetics , Bees/physiology , Biological Evolution , Cooperative Behavior , Isoptera/genetics , Isoptera/physiology , Nesting Behavior/physiology , Phenotype
3.
Clin Radiol ; 74(12): 974.e1-974.e6, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31521327

ABSTRACT

AIM: To compare a standard intra-operative mammography (IM) device with digital breast tomosynthesis using a dedicated device (Mozart system) in the evaluation of surgical margins at first excision. MATERIALS AND METHODS: The study received institutional review board approval and written informed consent was obtained from participants. From January 2018 to December 2018, a prospective analysis of the images of IM device and intra-operative digital breast tomosynthesis with a dedicated device (Mozart system) in n=89 breast cancer patients (average patients age: 58 years, age range: 35-76 years) was undertaken. Images were evaluated by two expert breast radiologists independently of each other and blinded to each other's interpretation, who indicated the positive cases requiring surgical re-excision intra-operatively. RESULTS: Mean cancer size was 12.5±4.5 mm. Radiological signs of the lesions were microcalcifications (n=71), nodules (n=10), and architectural distortions (n=8). A total of 20/89 (17%) patients underwent intra-operative re-excision for positive margins. Intra-operative digital breast tomosynthesis with a dedicated device and IM showed discrepancies in 15/89 cases (17%). Mozart system results informed the necessity to perform a re-excision (n=15). Overall, receiver operating characteristic (ROC) curve analysis showed and area under the ROC curve (AUC) of 0.82 for the Mozart system versus 0.65 for IM. ROC analysis of radiological findings with microcalcifications showed an AUC of 0.92 for the Mozart system versus 0.74 for IM, whereas AUC in cases with no microcalcifications were 0.87 and 0.75, respectively. CONCLUSION: Intra-operative digital breast tomosynthesis with a dedicated device provides more information (better accuracy) than IM and facilitated a reduction in re-excision rates.


Subject(s)
Breast Neoplasms/diagnostic imaging , Mammography , Margins of Excision , Adult , Aged , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Calcinosis/diagnostic imaging , Female , Humans , Intraoperative Period , Mammography/methods , Mastectomy, Segmental/methods , Middle Aged
4.
Vet Pathol ; 54(4): 710-719, 2017 07.
Article in English | MEDLINE | ID: mdl-28178427

ABSTRACT

Enterohemorrhagic Escherichia coli (EHEC) are strains of E. coli that express Shiga toxins (Stx) and cause hemorrhagic colitis. In some cases, disease can progress to hemolytic uremic syndrome, a potentially fatal form of kidney disease. Both enteric and renal disease are associated with the expression of stx genes, which are often carried on lysogenic phage. Toxin is expressed following induction and conversion of the phage to lytic growth. The authors previously used a germ-free mouse model to demonstrate that toxin gene expression is enhanced during growth in vivo and that renal disease is dependent on both prophage induction and expression of Stx2. In the current study, the authors document and quantify necrotizing colitis, examine the progression of enteric and renal disease, and determine the role of Stx2, phage genes, and the type 3 secretion system (T3SS) in bacterial colonization and colitis and systemic disease. By 1 day after inoculation, EHEC-monocolonized mice developed colitis, which decreased in severity thereafter. Systemic disease developed subsequently. Infection with EHEC mutant strains revealed that renal failure and splenic necrosis were absolutely dependent on the expression of Stx2 but that T3SS function and prophage excision were not necessary for systemic disease. In contrast, colitis was only partly dependent on Stx2. This study demonstrates that in germ-free mice, like in human patients, EHEC causes early colitis followed by renal failure and that systemic disease but not colitis is Stx2 dependent.


Subject(s)
Colitis/veterinary , Escherichia coli Infections/veterinary , Escherichia coli O157 , Rodent Diseases/microbiology , Shiga Toxin 2/toxicity , Animals , Colitis/microbiology , Colitis/pathology , Colon/microbiology , Colon/pathology , Enzyme-Linked Immunosorbent Assay , Escherichia coli Infections/microbiology , Escherichia coli Infections/pathology , Female , Germ-Free Life , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Male , Mice , Necrosis , Rodent Diseases/pathology , Shiga Toxin 2/metabolism
5.
Scand J Med Sci Sports ; 26(3): 299-306, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25735821

ABSTRACT

The purpose of this study was to examine the effectiveness of an active rehabilitation intervention for adolescents who are slow-to-recover after a sport-related concussion. Ten adolescents (three girls and seven boys) seen at the Montreal Children's Hospital Concussion Clinic participated in this case series. Adolescents who were symptomatic more than 4 weeks after the injury were provided with an active rehabilitation intervention (M = 7.9 weeks following injury; range = 3.7 to 26.2 weeks). The rehabilitation program includes gradual, closely monitored light aerobic exercise, general coordination exercises, mental imagery, as well as reassurance, normalization of recovery, and stress/anxiety reduction strategies. The program continued until complete symptom resolution and readiness to begin stepwise return to activities. The primary outcome of the study was evolution of post-concussion symptoms. Secondary outcomes included mood, energy, balance, and cognition. After the intervention, post-concussion symptoms significantly decreased for the group of participants. They also had decreased fatigue and improved mood after 6 weeks of initiating the rehabilitation intervention. This case series shows that postconcussive symptoms and functioning in adolescents following sports-related concussion can be improved after participation in an active rehabilitation intervention. The introduction of graded light intensity exercise in the post-acute period following concussion is safe, feasible and appears to have a positive impact on adolescents' functioning.


Subject(s)
Athletic Injuries/rehabilitation , Brain Concussion/rehabilitation , Post-Concussion Syndrome/prevention & control , Adolescent , Anxiety/prevention & control , Cognition , Exercise Therapy , Fatigue , Female , Humans , Male , Pilot Projects , Post-Concussion Syndrome/diagnosis , Postural Balance
6.
Am J Physiol Cell Physiol ; 309(5): C332-47, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-26108665

ABSTRACT

The potent trypanolytic properties of human apolipoprotein L1 (APOL1) can be neutralized by the trypanosome variant surface antigen gene product known as serum resistance-associated protein. However, two common APOL1 haplotypes present uniquely in individuals of West African ancestry each encode APOL1 variants resistant to serum resistance-associated protein, and each confers substantial resistance to human African sleeping sickness. In contrast to the dominantly inherited anti-trypanosomal activity of APOL1, recessive inheritance of these two trypanoprotective APOL1 alleles predisposes to kidney disease. Proposed mechanisms of APOL1 toxicity have included BH3 domain-dependent autophagy and/or ion channel activity. We probed these potential mechanisms by expressing APOL1 in Xenopus laevis oocytes. APOL1 expression in oocytes increased ion permeability and caused profound morphological deterioration (toxicity). Coexpression of BCL2 family members rescued APOL1-associated oocyte toxicity in the order MCL1 ∼ BCLW > BCLXL ∼ BCL2A1 ≫ BCL2. Deletion of nine nominal core BH3 domain residues abolished APOL1-associated toxicity, but missense substitution of the same residues abolished neither oocyte toxicity nor its rescue by coexpressed MCL1. The APOL1 BH3 domain was similarly dispensable for the ability of APOL1 to rescue intact mice from lethal trypanosome challenge. Replacement of most extracellular Na(+) by K(+) also reduced APOL1-associated oocyte toxicity, allowing demonstration of APOL1-associated increases in Ca(2+) and Cl(-) fluxes and oocyte ion currents, which were similarly reduced by MCL1 coexpression. Thus APOL1 toxicity in Xenopus oocytes is BH3-independent, but can nonetheless be rescued by some BCL2 family proteins.


Subject(s)
Apolipoproteins/biosynthesis , Apolipoproteins/toxicity , Lipoproteins, HDL/biosynthesis , Lipoproteins, HDL/toxicity , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Amino Acid Sequence , Animals , Apolipoprotein L1 , Apolipoproteins/genetics , Female , Humans , Lipoproteins, HDL/genetics , Mice , Molecular Sequence Data , Protein Structure, Tertiary/physiology , Proto-Oncogene Proteins c-bcl-2/genetics , Xenopus laevis
7.
Intern Med J ; 45(5): 576-80, 2015 May.
Article in English | MEDLINE | ID: mdl-25955463

ABSTRACT

This study assessed infection prevention and antimicrobial stewardship (AMS) practices in Australian residential aged-care facilities (RACF). Two hundred and sixty-five surveys (15.6%) were completed with all states represented and the majority (177 (67.3%)) privately run. Only 30.6% RACF had infection control trained staff on site. Few facilities had AMS policies, only 14% had antimicrobial prescribing restrictions. Most facilities offered vaccination to residents (influenza vaccination rates >75% in 73% of facilities), but pneumococcal vaccination was poor.


Subject(s)
Guideline Adherence , Homes for the Aged/standards , Infection Control/standards , Influenza, Human/prevention & control , Pneumonia, Pneumococcal/prevention & control , Residential Facilities/standards , Vaccination/statistics & numerical data , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Australia/epidemiology , Disease Outbreaks/prevention & control , Disease Outbreaks/statistics & numerical data , Female , Guideline Adherence/statistics & numerical data , Health Care Surveys , Homes for the Aged/statistics & numerical data , Humans , Influenza, Human/epidemiology , Male , Pneumonia, Pneumococcal/epidemiology , Population Surveillance , Practice Guidelines as Topic , Quality Improvement , Residential Facilities/statistics & numerical data , Vulnerable Populations
8.
Can J Infect Dis Med Microbiol ; 26(5): 268-72, 2015.
Article in English | MEDLINE | ID: mdl-26600816

ABSTRACT

BACKGROUND: The incidence of syphilis in Ottawa, Ontario, has risen substantially since 2000 to six cases per 100,000 in 2003, again to nine cases per 100,000 in 2007, and recently rose to 11 cases per 100,000 in 2010. The number of cases reported in the first quarter of 2010 was more than double that in the first quarter of 2009. OBJECTIVE: In May 2010, the Ontario Ministry of Health and Long Term Care requested the assistance of the Field Epidemiology Program to describe the increase in infectious syphilis rates and to identify social network sources and prevention messages. METHODS: Syphilis surveillance data were routinely collected from January 1, 2009 to July 15, 2010, and social networks were constructed from an enhanced social network questionnaire. Univariate comparisons between the enhanced surveillance group and the remaining cases from 2009 on non-normally distributed data were conducted using Kruskal-Wallis tests and χ(2) tests. RESULTS: The outbreak cases were comprised of 89% men. Seventeen of the 19 most recent cases consented to answer the questionnaire, which revealed infrequent use of condoms, multiple sex partners and sex with a same-sex partner. Information regarding social venues where sex partners were met was plotted together with sexual partnerships, linking 18 cases and 40 contacts, representing 37% of the outbreak population and connecting many of the single individuals and dyads. CONCLUSION: Uncovering the places sex partners met was an effective proxy measure of high-risk activities shared with infected individuals and demonstrates the potential for focusing on interventions at one named bar and one Internet site to reach a high proportion of the population at risk.


HISTORIQUE: L'incidence de syphilis à Ottawa, en Ontario, a beaucoup augmenté depuis 2000, passant de six cas sur 100 000 habitants en 2003 à neuf cas sur 100 000 habitants en 2007, puis à 11 cas sur 100 000 habitants en 2010. Le nombre de cas signalés pendant le premier trimestre de 2010 a plus que doublé par rapport à celui du premier trimestre de 2009. OBJECTIF: En mai 2010, le ministère de la Santé et des Soins de longue durée de l'Ontario a demandé l'aide du Programme canadien d'épidémiologie de terrain pour décrire l'augmentation du taux de syphilis infectieuses, en déterminer l'origine dans les réseaux sociaux et établir les messages de prévention. MÉTHODOLOGIE: Les chercheurs ont colligé systématiquement les données de surveillance sur la syphilis entre le 1er janvier 2009 et le 15 juillet 2010 et en ont établi les réseaux sociaux à partir d'un questionnaire amélioré sur les réseaux sociaux. Au moyen du test de Kruskal-Wallis et des tests du chi carré, ils ont effectué des comparaisons univariées des données non distribuées normalement entre le groupe de surveillance améliorée et les autres cas de 2009. RÉSULTATS: Les cas d'éclosion se composaient de 89 % d'hommes. Dix-sept des 19 cas les plus récents ont consenti à répondre au questionnaire, qui a révélé un usage peu fréquent du condom, de multiples partenaires sexuels et des relations sexuelles avec des partenaires de même sexe. Les chercheurs ont transcrit sur un graphique l'information relative aux lieux où les partenaires sexuels se sont rencontrés, ce qui a permis de relier 18 cas et 40 contacts, soit 37 % de la population de l'éclosion, et d'associer de nombreux individus uniques et de dyades. CONCLUSION: La découverte des lieux où les partenaires sexuels se sont rencontrés s'est révélée une mesure indirecte efficace des activités à haut risque partagées avec des personnes infectées et a démontré le potentiel d'intervenir seulement dans un bar précis et un site Internet donné pour joindre une forte proportion de la population à risque.

9.
Front Psychol ; 15: 1354544, 2024.
Article in English | MEDLINE | ID: mdl-39135866

ABSTRACT

Youth with developmental and pre-existing mental health conditions have been particularly vulnerable to declines in psychological functioning during the COVID-19 pandemic. This study aimed to first, analyze service usage within an outpatient child and adolescent psychiatry clinic in the months preceding and during the COVID-19 pandemic, and second, to examine associations with potential protective factors against mental health concerns in a treatment-engaged sample. Service usage was examined using clinic billing data, and reports on protective factors were gathered via parent survey of 81 children ages 6-17 years who received mental health treatment in an outpatient psychiatry clinic during the pandemic. Protective factors were assessed at the individual, family, and community levels, and included children's use of coping strategies, parental resilience, and parents' perceived social supports. Study outcomes, including mental health concerns, mental health emergencies, pandemic-related distress, and social impact of the pandemic, were analyzed via Pearson correlations and simultaneous multiple linear regressions. Findings suggest increased service usage and child coping, parental resilience, and social connectedness as factors associated with fewer mental health concerns in youth with psychiatric concerns during the pandemic. This study lends support for expanding psychiatric services with continued use of telemedicine platforms. Further, findings suggest a mental health benefit to optimizing individual, parental, and community-based resources to enhance children's psychological functioning, particularly for youth with pre-existing mental health conditions.

10.
J Clin Microbiol ; 51(12): 4083-6, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24088854

ABSTRACT

Here, we compare the sensitivities and times to detection (TTD) of BacT/Alert Pediatric FAN (PF) and Bactec Peds Plus blood culture bottles. Test bottles were inoculated with 2 ml of banked whole blood, 1-ml aliquots of antibiotic suspension, and organisms diluted to simulate a bacteremia level of 10 to 100 CFU/ml. The control bottles were inoculated with 3 ml of banked blood and organism suspensions only. The organism-drug combinations were Staphylococcus epidermidis and vancomycin, methicillin-resistant Staphylococcus aureus and vancomycin, Streptococcus pneumoniae, vancomycin, and ceftriaxone, Streptococcus agalactiae, ampicillin, and cefotaxime, Escherichia coli, cefotaxime, and cefepime, Pseudomonas aeruginosa, piperacillin-tazobactam, cefepime, and gentamicin, Neisseria meningitidis and ceftriaxone, and Haemophilus influenzae and ceftriaxone. The control and test bottle combinations were tested in duplicate. The bottles were incubated for 5 days; 32 control and 104 test bottles were incubated. Overall, the bacterial recovery rates for the PF and Peds Plus bottles were 37% and 62%, 94% and 100% in the controls, 19% and 50% in the test bottles, and 33% and 92% in the bottles with vancomycin, respectively. No bacteria were recovered from the bottles with S. pneumoniae, S. agalactiae, E. coli, N. meningitidis, or H. influenzae in combination with cefotaxime or ceftriaxone. The Peds Plus system detected P. aeruginosa in bottles with cefepime and piperacillin-tazobactam, but the PF system recovered bacteria only in bottles with trough levels of piperacillin-tazobactam. The mean TTD were shorter in the Peds Plus system controls (14.2 versus 18.0 h; P = 0.001) and the test bottles (14.3 versus 17.8 h; P = 0.008) than in the PF bottles. Overall, we demonstrated superior sensitivity, TTD, and antibiotic neutralization in the Bactec Peds Plus system compared to those in the Pediatric FAN system.


Subject(s)
Anti-Bacterial Agents/blood , Bacteremia/diagnosis , Bacteria/classification , Bacteria/isolation & purification , Bacteriological Techniques/methods , Blood/microbiology , Specimen Handling/methods , Humans , Sensitivity and Specificity , Time Factors
11.
Am J Transplant ; 12(7): 1924-8, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22487534

ABSTRACT

Apolipoprotein L-1 (APOL1) gene variants are associated with end-stage renal disease in African Americans (AAs). Here we investigate the impact of recipient APOL1 gene distributions on kidney allograft outcomes. We conducted a retrospective analysis of 119 AA kidney transplant recipients, and found that 58 (48.7%) carried two APOL1 kidney disease risk variants. Contrary to the association seen in native kidney disease, there is no difference in allograft survival at 5-year posttransplant for recipients with high-risk APOL1 genotypes. Thus, we were able to conclude that APOL1 genotypes do not increase risk of allograft loss after kidney transplantations, and carrying 2 APOL1 risk alleles should not be an impediment to transplantation.


Subject(s)
Apolipoproteins/genetics , Black People/genetics , Graft Survival/genetics , Kidney Transplantation , Lipoproteins, HDL/genetics , Adult , Apolipoprotein L1 , Genotype , Humans , Middle Aged
12.
Mol Ecol ; 26(4): 975-976, 2017 02.
Article in English | MEDLINE | ID: mdl-28239928
13.
Lupus ; 21(5): 559-62, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22140143

ABSTRACT

Congenital complete heart block associated with transplacental passage of maternal autoantibodies reactive with SSA/Ro and SSB/La is a rare disease with significant fetal, neonatal, and childhood morbidity and mortality. We present the case of dichorionic, diamniotic twins (female twin A and male twin B) exposed to maternal Ro and La autoantibodies with different disease expression. Twin A (female) had Mobitz type I second degree atrioventricular (AV) block (Wenckebach); twin B (male) had normal sinus rhythm. Both twins had structurally normal hearts but demonstrated echocardiographic evidence of endocardial fibroelastosis (EFE). Following maternal dexamethasone 4 mg once daily, twin A reverted to sinus rhythm in utero; twin B remained in sinus rhythm throughout pregnancy. Echocardiograms after delivery demonstrated resolution of EFE in both fetuses, and EKGs confirmed sinus rhythm. However, at five months of age, Holter monitor demonstrated first degree AV block and intermittent Wenckebach in twin A. Twin B remains in sinus rhythm. This case is one of only three in the literature that describes Mobitz type I second degree atrioventricular block presenting in fetuses exposed to maternal SSA and SSB autoantibodies and is the first case that we have seen reported in twins. Importantly, this case also adds to the growing body of literature describing EFE as a presentation of neonatal lupus with or without conduction system abnormalities, emphasizes the spectrum of cardiac conduction abnormalities in neonatal lupus syndrome, and raises interesting questions about discordant disease expression in twins.


Subject(s)
Antibodies, Antinuclear/immunology , Atrioventricular Block/etiology , Lupus Erythematosus, Systemic/congenital , Pregnancy Complications/immunology , Atrioventricular Block/physiopathology , Dexamethasone/therapeutic use , Echocardiography , Female , Follow-Up Studies , Glucocorticoids/therapeutic use , Humans , Infant , Infant, Newborn , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/immunology , Male , Pregnancy , Twins , Young Adult
14.
J Neonatal Perinatal Med ; 15(4): 753-758, 2022.
Article in English | MEDLINE | ID: mdl-35811547

ABSTRACT

BACKGROUND: Small for gestational age (SGA) infants are likely to have decreased placental transfer of opioids and other substances and lower amounts of fat deposition, hence less severe neonatal abstinence syndrome (NAS). The goal of this study is to correlate SGA status and severity of NAS in infants admitted to the neonatal intensive care unit (NICU). METHODS: This is a retrospective analysis of term and late-preterm infants (≥35 weeks gestation) exposed to in-utero substances, born between September 2006 and May 2021, and admitted to an inner-city NICU for medical therapy for NAS. Indicators of the severity of NAS (duration of medical treatment, duration of hospitalization, use of phenobarbital, and use of clonidine) were compared between infants characterized as SGA (birth weight <10th percentile for gestational age) to those not categorized as SGA (non-SGA). RESULTS: A total of 992 infants met the study criteria; 205 (20.7%) in the SGA group and 787 (79.3%) in the non-SGA group. The median duration of medical treatment was significantly lower in infants in the SGA group (22 days vs. 26 days, p = 0.04) and they were less likely to be treated with phenobarbital (19% vs. 26.8%, p = 0.02). CONCLUSION: SGA infants displayed less severe NAS symptoms as indicated by shorter a duration of medical treatment and decreased need for phenobarbital. Our findings may impact decisions around identifying the optimum treatment protocols catered to SGA infants with NAS.


Subject(s)
Infant, Premature , Neonatal Abstinence Syndrome , Infant, Newborn , Humans , Pregnancy , Infant , Female , Gestational Age , Retrospective Studies , Neonatal Abstinence Syndrome/drug therapy , Placenta , Phenobarbital/therapeutic use
15.
Lymphology ; 55(4): 167-177, 2022.
Article in English | MEDLINE | ID: mdl-37553005

ABSTRACT

Breast-conserving surgery (BCS) is the standard of care for early-stage breast cancer. We retrospectively enrolled 530 patients (mean age: 62.96 ± 12.69 years) undergoing BCS between January 1, 2018, and December 31, 2019. During the COVID-19 pandemic, all patients with at least 1 year of follow-up were telephonically asked after surgery to provide clinical signs and symptoms attributable to postoperative breast cancer-related lymphedema of the breast (BCRL-B). Thirty-one (5.8%) patients reported breast edema and were visited to measure the tissue dielectric constant (TDC) and to assess the induration of the skin. There was a difference seen in treatment with lumpectomy + ALND performed more frequently in patients with (29%) than without (12%) BCRL-B. In the subgroup of patients with BCRL-B (n=31), significantly higher values of local total water were calculated in the nine patients who underwent Lump + ALND procedure (1.86 ± 0.48 vs. 1.48 ± 0.38; p = 0.046). Among patients with BCRL-B (n=31), in eight patients (25.8%) tissue induration measured with SkinFibroMeter was >0.100 N, thus suggesting tissue fibrosis. Cumulative survival probability at 1-year after surgery was 0.992. No statistical differences in 1-year survival after surgery were found for type of surgery (p = 0.890) or absence/presence of BCRL-B (p = 0.480). In univariate logistic regression, only lumpectomy + ALND surgery (p = 0.009) and any subsequent axillary lymph node removal surgery (p = 0.003) were associated with BCRL-B. Both of these variables were also found to be statistically significant in the multivariate regression model. Further prospective research is warranted to analyze potentential predictors of BCRL-B and to reduce/ prevent this complication.

16.
Nat Cell Biol ; 1(5): 293-7, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10559942

ABSTRACT

Conventional kinesin transports membranes along microtubules in vivo, but the majority of cellular kinesin is unattached to cargo. The motility of non-cargo-bound, soluble kinesin may be repressed by an interaction between the amino-terminal motor and carboxy-terminal cargo-binding tail domains, but neither bead nor microtubule-gliding assays have shown such inhibition. Here we use a single-molecule assay that measures the motility of kinesin unattached to a surface. We show that full-length kinesin binds microtubules and moves about ten times less frequently and exhibits discontinuous motion compared with a truncated kinesin lacking a tail. Mutation of either the stalk hinge or neck coiled-coil domain activates motility of full-length kinesin, indicating that these regions are important for tail-mediated repression. Our results suggest that the motility of soluble kinesin in the cell is inhibited and that the motor becomes activated by cargo binding.


Subject(s)
Kinesins/chemistry , Kinesins/physiology , Microtubules/physiology , Amino Acid Sequence , Amino Acid Substitution , Animals , Cell Line , Kinesins/genetics , Molecular Sequence Data , Movement , Mutagenesis, Site-Directed , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Spodoptera , Transfection
17.
Org Biomol Chem ; 9(20): 7126-33, 2011 Oct 21.
Article in English | MEDLINE | ID: mdl-21879130

ABSTRACT

A limited range of redox-active, rotaxane-based, molecular switches exist, despite numerous potential applications for them as components of nanoscale devices. We have designed and synthesised a neutral, redox-active [2]rotaxane, which incorporates an electron-deficient pyromellitic diimide (PmI)-containing ring encircling two electron-rich recognition sites in the form of dioxynaphthalene (DNP) and tetrathiafulvalene (TTF) units positioned along the rod section of its dumbbell component. Molecular modeling using MacroModel guided the design of the mechanically interlocked molecular switch. The binding affinities in CH(2)Cl(2) at 298 K between the free ring and two electron-rich guests--one (K(a) = 5.8 × 10(2) M(-1)) containing a DNP unit and the other (K(a) = 6.3 × 10(3) M(-1)) containing a TTF unit--are strong: the one order of magnitude difference in their affinities favouring the TTF unit suggested to us the feasibility of integrating these three building blocks into a bistable [2]rotaxane switch. The [2]rotaxane was obtained in 34% yield by relying on neutral donor-acceptor templation and a double copper-catalysed azide-alkyne cycloaddition (CuAAC). Cyclic voltammetry (CV) and spectroelectrochemistry (SEC) were employed to stimulate and observe switching by this neutral bistable rotaxane in solution at 298 K, while (1)H NMR spectroscopy was enlisted to investigate switching upon chemical oxidation. The neutral [2]rotaxane is a chemically robust and functional switch with potential for applications in device settings.


Subject(s)
Rotaxanes/chemistry , Cyclization , Molecular Structure , Oxidation-Reduction
18.
J Exp Med ; 174(3): 525-37, 1991 Sep 01.
Article in English | MEDLINE | ID: mdl-1908508

ABSTRACT

To study the association of autoimmunity and human B cell neoplasia, we have established a model of a B cell lymphoma which expresses a pathogenic autoantibody of defined specificity. The Ig VH gene expressed in this neoplasm was analyzed longitudinally using clinical specimens taken from the splenic lymphoma (S) at diagnosis and from lymph node relapses 3 and 4 yr later (N3 and N4). Southern analysis and oligonucleotide hybridization experiments demonstrated that clonally related predominant and minor tumor cell populations were present in S at diagnosis, and that the minor population became the predominant population in the relapse specimens, N3 and N4. Although the Ig specificity and idiotype were the same at diagnosis and at both relapses, analysis of the expressed VH gene sequences showed 14 base changes between S and N3, and 2 further changes at N4. Little sequence heterogeneity was observed at each sampling time, indicating that the ongoing mutation frequency was low. The relevant germline precursor VH gene was determined from autologous germline DNA and compared to the expressed genes. Based on the pattern of shared and unshared mutations, we were able to establish the genealogic relationship of the germline VH gene and the expressed clonotypes of S, N3 and N4. Taken together, the findings from Southern blotting, oligonucleotide hybridization, and sequence analysis permit us to describe a molecular aspect of tumor progression, "clonotypic shift", wherein subpopulations of the malignant clone, marked by different V gene clonotypes, emerge and predominate at different time points in the evolution of the lymphoma. Furthermore, the sequential and nonrandom pattern of the VH mutations, correlated with the observed conservation of autospecificity and idiotype, implies that clonal selection may have influenced the pathogenesis of the lymphoma.


Subject(s)
Anemia, Hemolytic, Autoimmune/immunology , Gene Rearrangement, B-Lymphocyte, Heavy Chain , Immunoglobulin Heavy Chains/genetics , Lymphoma, B-Cell/immunology , Amino Acid Sequence , Anemia, Hemolytic, Autoimmune/complications , Autoantigens/immunology , Base Sequence , Blotting, Southern , Clone Cells , Genes, Immunoglobulin , Humans , Immunoglobulin Idiotypes/immunology , Lymphoma, B-Cell/complications , Molecular Sequence Data , Mutation , Oligonucleotides/chemistry , Polymerase Chain Reaction , Time Factors
19.
Cephalalgia ; 30(12): 1524-6, 2010 Dec.
Article in English | MEDLINE | ID: mdl-19614705

ABSTRACT

Brain stem structures are implicated in the generation of migraine and other types of headache. The patient described herein had chronic left hemicranial headaches associated with a left pontine infarction.


Subject(s)
Brain Stem Infarctions/complications , Headache/etiology , Pons/pathology , Brain Stem Infarctions/pathology , Brain Stem Infarctions/physiopathology , Female , Headache/pathology , Headache/physiopathology , Humans , Hypertension/complications , Incidental Findings , Middle Aged , Pituitary Neoplasms/complications , Pituitary Neoplasms/surgery , Prolactinoma/complications , Prolactinoma/surgery
20.
Ophthalmic Epidemiol ; 27(3): 226-236, 2020 06.
Article in English | MEDLINE | ID: mdl-32079450

ABSTRACT

Purpose: To examine factors decreasing participation in school-based vision programs from parent and teacher perspectives.Methods: We conducted 41 semi-structured focus groups (20 parent groups, 21 teacher/staff groups), at 10 Baltimore and 11 Chicago public elementary and middle schools offering school-based vision programs. School-based vision programs provided vision screening, eye exams, and eyeglasses if needed. Focus groups ranged in size from 2-9 participants (median = 5). Sessions were recorded, transcribed, and coded through an iterative process to develop themes using inductive analysis.Results: Ninety parents and 117 teachers/staff participated. Participants identified five major factors decreasing participation in school-based vision programs: (1) challenges with the consent form, including distribution, collection, and literacy and language barriers; (2) having existing eye care; (3) misunderstandings about the program, especially related to cost and insurance; (4) difficulty raising parental awareness of the program; and (5) certain attitudes towards vision, eye care, and school-based programs, including low prioritization of eye care, mistrust of the program, fear of sharing private information, not believing their child needs glasses, and reluctance accepting 'subsidized' services.Conclusion: Parents and teachers identified important structural barriers to participation (i.e., consent form challenges and low parental awareness) and specific reasons for non-participation (i.e., attitudes, misunderstanding of the program, existing eye care) in school-based vision programs. Effective strategies are needed to facilitate return of consent forms and promote awareness of school-based vision programs among parents. Programs should also target services towards those currently without access to eye care and increase awareness about paediatric vision needs.


Subject(s)
Parents/psychology , Refractive Errors/diagnosis , School Health Services/standards , School Teachers/psychology , Vision Screening/methods , Adolescent , Adult , Aged , Attitude to Health , Awareness , Child , Child, Preschool , Eyeglasses , Focus Groups/methods , Health Services Accessibility/statistics & numerical data , Humans , Middle Aged , Qualitative Research , Refractive Errors/epidemiology , School Health Services/statistics & numerical data , School Teachers/statistics & numerical data , Schools/statistics & numerical data , Young Adult
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