Land management explains major trends in forest structure and composition over the last millennium in California's Klamath Mountains.

SignificanceWe provide the first assessment of aboveground live tree biomass in a mixed conifer forest over the late Holocene. The biomass record, coupled with local Native oral history and fire scar records, shows that Native burning practices, along with a natural lightning-based fire regime, promoted long-term stability of the forest structure and composition for at least 1 millennium in a California forest. This record demonstrates that climate alone cannot account for observed forest conditions. Instead, forests were also shaped by a regime of frequent fire, including intentional ignitions by Native people. This work suggests a large-scale intervention could be required to achieve the historical conditions that supported forest resiliency and reflected Indigenous influence.

Campylobacter in recreational lake water in southern Quebec, Canada: presence, concentration, and association with precipitation and ruminant farm proximity.

Campylobacter is an important cause of gastrointestinal illness and exposure to recreational water is one potential source of infection. The objective of this study was to investigate the presence and concentrations of Campylobacter, and determine the influence of agricultural activities and precipitation on their presence, at lake beaches used for water recreation in southern Quebec, Canada. A total of 413 water samples were collected from June to August, from 22 beaches, between 2011 and 2013. The overall proportion of positive water samples was estimated to be 33.9% (95% CI: 27.7, 40.1) for C. jejuni and 49.7% (95% CI: 41.8, 57.6) for Campylobacter spp. The concentrations of both thermotolerant Campylobacter spp. and C. jejuni ranged from 20 to 900 bacteria/L of water. Logistic regressions showed that the presence of C. jejuni and Campylobacter spp. was significantly associated with the year and season. Other significant predictors of C. jejuni, but not Campylobacter spp., included the presence of precipitation the day before sampling and the presence of ruminant farms within a 5 km radius of the beach. The present study provides insights into the risk of Campylobacter presence in recreational lake water for better understanding public health risks.

Long-Term Health-Related Quality of Life Outcomes in Digital Replantation versus Revision Amputation.

Background Earlier, digit viability judged the success of digital replantation. Now, utility health-related quality of life (HRQOL) measures can better assess the impact of digital replantation. Methods Overall, 264 digital injury patients were sent a regimen of utility measures: Disabilities of the Arm, Shoulder and Hand (DASH) score, European Quality of Life 5 Dimensions, visual analog scale (VAS), time trade-off (TTO), and standard gamble (SG). Overall, 51 patients responded completely to all of these-36 replantation patients and 15 revision amputation patients. The utility results of these patients were stratified between replantation versus revision amputation; dominant hand replantation versus nondominant hand replantation; and dominant hand revision amputation versus nondominant hand revision amputation. Results The mean VAS score of replant (0.84) and revision amputation (0.75) groups was significantly different (p = 0.05). The mean DASH score of dominant hand replantations (29.72) and nondominant hand replantations (17.97) was significantly different (p = 0.027). The dominant hand revision amputation had higher anxiety levels in comparison to nondominant hand revision amputation (p = 0.027). Patients with two or more digits replanted showed a significant decrease in VAS, TTO, and SG scores in comparison to patients who only had one digit replanted (p = 0.009, 0.001, and 0.001, respectively). Conclusions This study suggests that HRQOL can offer better indices for outcomes of digital replantation. This shows some specific replantation cohorts have a significantly better quality of life when compared with their specific correlating revision amputation cohort. These findings can be employed to further refine indications and contraindications to replantation and help predict the quality of life outcomes.

Lymphaticovenous Anastomosis and Vascularized Lymph Node Transfer for the Treatment of Lymphedema-A Canadian Case Series.

Introduction: Lymphedema is a chronic and debilitating condition. This study aims to assess the efficacy and safety of lymphaticovenous anastomosis (LVA) and vascularized lymph node transfers (VLNT) for the treatment of patients suffering from lymphedema, mainly by comparing pre- and postoperative daily compression use, limb volumes, and occurrence of cellulitis. Methods: We performed a retrospective analysis of patients who were treated by a single surgeon for lymphedema with LVA and/or VLNT between March 2018 and February 2020. Eighteen limbs met the inclusion criteria. The severity of lymphatic dysfunction was assessed by indocyanine green lymphangiography. Patients with patent vessels were offered LVA, whereas those without were offered VLNT. Pre- and postoperative circumferential limb measurements, use of compression garments, and postoperative complications were compared. Results: Nine limbs underwent LVA, 8 underwent VLNT, and one both. The minimum follow-up was 12 months. Postoperatively, all but 3 patients (83%) were able to cease daily compression. When considering excess limb volumes, the average reduction was 58%. This reduction was achieved despite compression weaning. Forty-four percent of patients (8) reported episodes of recurrent cellulitis preoperatively, while postoperatively, only 3 of those patients (17%) experienced cellulitis, which was statistically significant (P = .018). No surgical complications occurred. Conclusions: Patients with lymphedema can benefit from LVA and VLNT surgery. An important effect of surgery is decreased dependence on daily compression garments to maintain a stable and reasonable limb volume. The reduction of limb circumference after 1 year was similar to LVA and VLNT. Episodes of cellulitis were significantly lower after the intervention.

Introduction : Le lymphœdème est une affection chronique et débilitante. La présente étude vise à évaluer l'efficacité et l'innocuité de l'anastomose lymphaticoveineuse (ALV) et des transferts des ganglions lymphatiques vascularisés (TGLV) pour le traitement des patients ayant un lymphœdème, surtout en comparant l'utilisation quotidienne des vêtements compressifs, le volume des membres et l'occurrence de cellulites avant et après l'opération. Méthodologie : Les chercheurs ont procédé à une analyse rétrospective des patients chez qui le même chirurgien a procédé à une ALV ou à un TGLV à cause d'un lymphœdème entre mars 2018 et février 2020. Dix-huit membres ont respecté les critères d'inclusion. Les chercheurs ont évalué la gravité du dysfonctionnement lymphatique par lymphangiographie au vert d'indocyanine. Les patients ayant des vaisseaux perméables se sont fait offrir une ALV, et les autres, un TGLV. Les chercheurs ont comparé les mesures du périmètre des membres et l'utilisation de vêtements compressifs avant et après l'opération, de même que les complications postopératoires. Résultats : Une ALV a été effectuée sur neuf membres, des TGLV, sur huit membres, et les deux interventions, sur un membre. La période de suivi minimale était de 12 mois. Après l'opération, tous les patients, sauf trois (83%), ont pu cesser la compression quotidienne. En moyenne, le volume excessif des membres a diminué de 58%. Les chercheurs ont obtenu cette réduction malgré le sevrage de la compression. Au total, 44% des patients (huit) ont signalé des récurrences de la cellulite avant l'opération, mais après l'opération, seulement trois d'entre eux (17%) en ont souffert, ce qui est statistiquement significatif. Aucune complication chirurgicale n'a été signalée. Conclusions : Les patients ayant un lymphœdème peuvent profiter d'une ALV ou d'un TGLV. Parmi ses effets importants, l'opération réduit la dépendance au port quotidien de vêtements compressifs afin que les membres conservent un volume stable et raisonnable. La réduction du paramètre des membres au bout d'un an était semblable après l'ALV et les TGLV. Les épisodes de cellulite étaient considérablement moins fréquents après l'intervention.

Normative data for the 12-item Buschke memory task in the Quebec-French population aged 50 and over.

OBJECTIVE: The 12-item Buschke memory test is used to assess verbal episodic memory in adults and older adults. However, there is no normative data for this test adjusted to the older Quebec-French population. The aim of the study was to produce normative data for the 12-item Buschke for the Quebec-French population aged 50 and older. METHOD: The normative sample consisted of 172 healthy French-speaking participants aged 50-89 years, from the Province of Quebec (Canada). The influence of age, years of formal education, and sex on five 12-item Buschke scores were analyzed. Based on the distribution of scores, normative data were developed as Z-scores equation, regression equation, and percentiles. RESULTS: Age, years of formal education, and sex were all associated with performance. Equations to calculate Z-scores were provided for the free recall trial 1 and the free recall trials 1-3. Stratified percentiles were provided for the delayed free recall and total recall 1-3. CONCLUSIONS: The normative data for the 12-item Buschke improve the accuracy of clinicians to detect verbal episodic memory impairments in Quebec's aging population.

Independent age estimates resolve the controversy of ancient human footprints at White Sands.

Human footprints at White Sands National Park, New Mexico, USA, reportedly date to between ~23,000 and 21,000 years ago according to radiocarbon dating of seeds from the aquatic plant Ruppia cirrhosa. These ages remain controversial because of potential old carbon reservoir effects that could compromise their accuracy. We present new calibrated 14C ages of terrestrial pollen collected from the same stratigraphic horizons as those of the Ruppia seeds, along with optically stimulated luminescence ages of sediments from within the human footprint-bearing sequence, to evaluate the veracity of the seed ages. The results show that the chronologic framework originally established for the White Sands footprints is robust and reaffirm that humans were present in North America during the Last Glacial Maximum.

Canadian Expert Opinion on Breast Reconstruction Access: Strategies to Optimize Care during COVID-19.

BACKGROUND: Breast reconstructive services are medically necessary, time-sensitive procedures with meaningful health-related quality of life benefits for breast cancer survivors. The COVID-19 global pandemic has resulted in unprecedented restrictions in surgical access, including access to breast reconstructive services. A national approach is needed to guide the strategic use of resources during times of fluctuating restrictions on surgical access due to COVID-19 demands on hospital capacity. METHODS: A national team of experts were convened for critical review of healthcare needs and development of recommendations and strategies for patients seeking breast reconstruction during the pandemic. Following critical review of literature, expert discussion by teleconference meetings, and evidenced-based consensus, best practice recommendations were developed to guide national provision of breast reconstructive services. RESULTS: Recommendations include strategic use of multidisciplinary teams for patient selection and triage with centralized coordinated use of alternate treatment plans during times of resource restrictions. With shared decision-making, patient-centered shifting and consolidation of resources facilitate efficient allocation. Targeted application of perioperative management strategies and surgical treatment plans maximize the provision of breast reconstructive services. CONCLUSIONS: A unified national approach to strategically reorganize healthcare delivery is feasible to uphold standards of patient-centered care for patients interested in breast reconstruction.

The polycomb group gene Bmi1 regulates antioxidant defenses in neurons by repressing p53 pro-oxidant activity.

Aging may be determined by a genetic program and/or by the accumulation rate of molecular damages. Reactive oxygen species (ROS) generated by the mitochondrial metabolism have been postulated to be the central source of molecular damages and imbalance between levels of intracellular ROS and antioxidant defenses is a characteristic of the aging brain. How aging modifies free radicals concentrations and increases the risk to develop most neurodegenerative diseases is poorly understood, however. Here we show that the Polycomb group and oncogene Bmi1 is required in neurons to suppress apoptosis and the induction of a premature aging-like program characterized by reduced antioxidant defenses. Before weaning, Bmi1(-/-) mice display a progeroid-like ocular and brain phenotype, while Bmi1(+/-) mice, although apparently normal, have reduced lifespan. Bmi1 deficiency in neurons results in increased p19(Arf)/p53 levels, abnormally high ROS concentrations, and hypersensitivity to neurotoxic agents. Most Bmi1 functions on neurons' oxidative metabolism are genetically linked to repression of p53 pro-oxidant activity, which also operates in physiological conditions. In Bmi1(-/-) neurons, p53 and corepressors accumulate at antioxidant gene promoters, correlating with a repressed chromatin state and antioxidant gene downregulation. These findings provide a molecular mechanism explaining how Bmi1 regulates free radical concentrations and reveal the biological impact of Bmi1 deficiency on neuronal survival and aging.

The LIM homeobox transcription factor Lhx2 is required to specify the retina field and synergistically cooperates with Pax6 for Six6 trans-activation.

In mammals, a limited set of homeobox-containing transcription factors are expressed in the presumptive eye field and required to initiate eye development. How these factors interact together at the genetic and molecular level to coordinate this developmental process is poorly understood. We found that the Lhx2 and Pax6 transcription factors operate in a concerted manner during retinal development to promote transcriptional activation of the Six6 homeobox-gene in primitive and mature retinal progenitors. Lhx2 demarcates the presumptive retina field at the neural plate stage and Lhx2 inactivation delays initiation of Rx, Six3 and Pax6 expression in this domain. The later expressed Six6 is properly activated in the pituitary/hypothalamic axis of Lhx2(-/-) embryos, but expression fails to be initiated in the optic vesicle. Lhx2 and Pax6 associate with the chromatin at several regions of Six6 in vivo and cooperate for trans-activation of Six6 regulatory elements in vitro. In retinal progenitor/stem cells, both Lhx2 and Pax6 are genetically required for proper Six6 expression and forced co-expression of Lhx2 and Pax6 can synergistically trans-activate the Six6 locus. Our work reveals how two master regulators of eye development coordinate their action to sequentially promote tissue-specific transcriptional initiation and full activation of a retinal determinant gene.

A comparison of sample weight and culture methods for the detection of Salmonella in pig feces.

Five protocols were compared to determine the combined effects of different sample weights and culture methods for the recovery of Salmonella from 310 pig cecal samples taken in abattoirs as part of the Canadian Integrated Program for Anti-microbial Resistance Surveillance. Sample weights evaluated were 1 and 10 g. Culture methods used with each sample weight were modified semisolid Rappaport-Vassiliadis agar (MSRV) and brilliant green agar with sulfa and novobiocin (BGSN) and xylose-lysine-tergitol-4 agar (XLT4). A preliminary sample preparation step in saline was also evaluated using a 10-g sample and MSRV. The Salmonella recovery rate varied from 20% for the saline MSRV 10-g protocol to 32% for the MSRV 10-g and the BGSN-XLT4 10-g protocols. A good agreement (K > 0.8) was observed between pairs of protocols except whenever the saline MSRV 10-g and the MSRV 1-g protocols were compared. Larger samples (10 g) yielded higher detection of Salmonella than 1-g samples for the MSRV protocol (32 versus 25%), whereas the differences were not statistically significant for the BGSN-XLT4 protocols. Protocols using the BGSN-XLT4 agar yielded higher detection rates of Salmonella compared with MSRV with 1-g samples (30 versus 25%), whereas it was equivalent with 10-g samples. Considering a greater recovery rate, the ease of use, and a better time and resource efficiency, the MSRV 10-g protocol was therefore adopted by the Canadian Integrated Program for Antimicrobial Resistance Surveillance.

Quantification of E. coli O157 and STEC in feces of farm animals using direct multiplex real time PCR (qPCR) and a modified most probable number assay comprised of immunomagnetic bead separation and qPCR detection.

To better understand Escherichia coli O157:H7 on-farm transmission dynamics requires sensitive methods for quantification of a broad range of concentrations of target organisms. For this purpose, a multiplex real time PCR (qPCR) assay was developed for quantification of O157 E. coli from 1g fecal samples of cattle and other animal species, targeting the Shiga toxin genes (stx1 and stx2) and the O157 somatic antigen gene, per. The multiplex qPCR assay provided specific detection across a broad range of bacterial concentrations with a lower limit of detection (LOD) of 10(1) genome copies which is equivalent to 10(1) bacteria. However, the LOD, when direct qPCR was applied to quantification of the targets in the feces of dairy cattle, was 10(3) genome copies per gram of feces. Enumeration below the threshold for direct qPCR was performed using a modified most probable number (mMPN) method whereby E. coli O157 in enriched samples was isolated using immunomagnetic bead separation (IMS) and detected using qPCR, thus reducing the time and logistic constraints of biochemical/serological/gel analysis. Application of the mMPN (IMS/qPCR) assay to samples that were negative when tested using direct qPCR alone permitted quantification of low levels of E. coli O157 below levels detectable with direct qPCR. The direct qPCR and mMPN (IMS/qPCR) assays were applied to fecal samples from dairy, beef, swine and poultry feces. This approach can be employed to gain a better understanding of the patterns of infection in animals for analysis of on-farm transmission dynamics, for evaluating the effects of on-farm control strategies and for risk assessment in public health.

Factors influencing enoxaparin anti-Xa activity in surgical critically ill patients.

STUDY OBJECTIVE: The objectives of the present study were to describe the incidence of low anti-Xa levels defined as below 0.1 IU/mL in a general surgical intensive care unit population and to evaluate factors independently influencing anti-Xa activity. DESIGN: A prospective study was undertaken. SETTING: Thirty-six patients admitted to a general intensive care unit and receiving subcutaneous (SC) enoxaparin 30 mg twice daily for thromboprophylaxis between November 2003 and August 2005 were included in the study. MEASUREMENTS AND MAIN RESULTS: After reaching steady state, anti-Xa activity was determined by chromogenic assay at 0, 3, 6, and 9 hours after injection. Anti-Xa levels below 0.1 IU/mL at any time were considered subtherapeutic. Areas under the curve (AUCs) for a 12-hour dosing interval were estimated. Factors influencing anti-Xa AUC were evaluated using linear regression. Two patients (5.6%) did not attain therapeutic levels defined as anti-Xa more than 0.1 IU/mL at 3 hours post dose. Median AUC was 1.84 IU·h/mL (interquartile range, 1.47 IU·h/mL). In the linear regression analysis, sex and creatinine clearance were significant predictors of anti-Xa AUC(0-12h) levels. CONCLUSION: In the study, prophylactic SC enoxaparin in critically ill patients at the current 30 mg SC twice daily dosage attained an anti-Xa level more than 0.1 U/mL in nearly all patients. In addition, low creatinine clearances and female sex are associated with higher anti-Xa activity AUC(0-12h).

Differential contribution of bacterial N-formyl-methionyl-leucyl- phenylalanine and host-derived CXC chemokines to neutrophil infiltration into pulmonary alveoli during murine pneumococcal pneumonia.

Despite the development of new potent antibiotics, Streptococcus pneumoniae remains the leading cause of death from bacterial pneumonia. Polymorphonuclear neutrophil (PMN) recruitment into the lungs is a primordial step towards host survival. Bacterium-derived N-formyl peptides (N-formyl-methionyl-leucyl-phenylalanine [fMLP]) and host-derived chemokines (KC and macrophage inflammatory protein 2 [MIP-2]) are likely candidates among chemoattractants to coordinate PMN infiltration into alveolar spaces. To investigate the contribution of each in the context of pneumococcal pneumonia, CD1, BALB/c, CBA/ca, C57BL/6, and formyl peptide receptor (FPR)-knockout C57BL/6 mice were infected with 10(6) or 10(7) CFU of penicillin/erythromycin-susceptible or -resistant serotype 3 or 14 S. pneumoniae strains. Antagonists to the FPR, such as cyclosporine H (CsH) and chenodeoxycholic acid, or neutralizing antibodies to KC and MIP-2 were injected either 1 h before or 30 min after infection, and then bronchoalveolar lavage fluids were obtained for quantification of bacteria, leukocytes, and chemokines. CsH was effective over a short period after infection with a high inoculum, while anti-CXC chemokine antibodies were effective after challenge with a low inoculum. CsH prevented PMN infiltration in CD1 mice infected with either serotype 3 or 14, whereas antichemokine antibodies showed better efficacy against the serotype 3 strain. When different mouse strains were challenged with serotype 3 bacteria, CsH prevented PMN migration in the CD1 mice only, whereas the antibodies were effective against CD1 and C57BL/6 mice. Our results suggest that fMLP and chemokines play important roles in pneumococcal pneumonia and that these roles vary according to bacterial and host genetic backgrounds, implying redundancy among chemoattractant molecules.

Pax6 is required for delta-catenin/neurojugin expression during retinal, cerebellar and cortical development in mice.

The transcription factor Pax6 regulates multiple aspects of central nervous system (CNS) development. At the cellular level, the Pax6 mutation was reported to affect homophilic and heterophilic cellular adhesion, neuron polarity and neurite outgrowth. These abnormalities were observed in multiple regions of Pax6-mutant CNS, suggesting a common function for Pax6 in regulating cytoskeletal dynamics. However, target genes mediating Pax6 function in cytoskeletal dynamics remain largely unknown. Using DNA microarrays, we identified delta-catenin (delta-catenin /neurojugin) as a potential direct target of Pax6 in the CNS. delta-catenin encodes a large cytoskeletal protein that localizes at adherens junction in the CNS and that can modulate neurite outgrowth and N-cadherin turnover. delta-catenin was found to be co-expressed with Pax6 in several regions of the developing CNS. In Pax6 mutant embryos, delta-catenin expression was severely reduced in the optic vesicle neural ectoderm, in the ventricular zone of the neocortex and in the external granule layer of the cerebellum. We identified a Pax6 binding site in delta-catenin promoter that is conserved between mice and humans and which is effectively bound by Pax6 in vitro. Our results suggest that Pax6 regulates delta-catenin expression during CNS development in mice.