Testing for t(3;8) in MYC/BCL6-rearranged large B-cell lymphoma identifies a high-risk subgroup with inferior survival.

ABSTRACT: A reciprocal t(3;8) BCL6::MYC fusion is common in large B-cell lymphoma (LBCL) with MYC and BCL6 disruption. These pseudo-double-hit cases are not adverse, whereas t(3;8)-MYC/BCL6 lymphoma has an inferior prognosis relative to other MYC-rearranged LBCL.

Change in Body Mass Index in Youth in the First 5 Years After Type 1 Diabetes Mellitus Diagnosis.

OBJECTIVE: Examine body mass index (BMI) trajectories in American youth with type 1 diabetes (T1D) over the first 5 years following diagnosis. METHODS: Retrospective record review of BMI trajectories in youth with T1D diagnosed in 2015 to 2016. RESULTS: Near the time of diabetes diagnosis, 35.5% of youth had BMIs in the overweight/obesity range. These rates increased over time (P < .001), with 52.8% having overweight/obesity 5 years after diagnosis. Average age when BMI rose from healthy to overweight/obese or overweight to obese (rise group) was at 12.7 years, occurring 2.5 years after diagnosis. There were no differences between hemoglobin A1c, use of continuous glucose monitors, or use of insulin pumps between the rise group and those with healthy BMI throughout the study period. CONCLUSIONS: Alarmingly high rates of overweight/obesity in youth were observed within 5 years following T1D diagnosis. Awareness and further research are necessary to address this independent risk factor for morbidities.

Recent advances in delivering free or nanoencapsulated Curcuma by-products as antimicrobial food additives.

Food commodities are often contaminated by microbial pathogens in transit or during storage. Hence, mitigation of these pathogens is necessary to ensure the safety of food commodities. Globally, researchers used botanicals as natural additives to preserve food commodities from bio-deterioration, and advances were made to meet users' acceptance in this domain, as synthetic preservatives are associated with harmful effects to both consumers and environments. Over the last century, the genus Curcuma has been used in traditional medicine, and its crude and nanoencapsulated essential oils (EOs) and curcuminoids were used to combat harmful pathogens that deteriorate stored foods. Today, more research is needed for solving the problem of pathogen resistance in food commodities and to meet consumer demands. Therefore, Curcuma-based botanicals may provide a source of natural preservatives for food commodities that satisfy the needs both of the food industry and the consumers. Hence, this article discusses the antimicrobial and antioxidant properties of EOs and curcuminoids derived from the genus Curcuma. Further, the action modes of Curcuma-based botanicals are explained, and the latest advances in nanoencapsulation of these compounds in food systems are discussed alongside knowledge gaps and safety assessment where the focus of future research should be placed.

Impact of routine preoperative 18 FDG PET/CT on the surgical management of primary colorectal cancer.

OBJECTIVES: Determine the usefulness of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (18 FDG-PET/CT) in the preoperative setting of colorectal cancer (CRC), assessing its impact on changes in management strategy. METHODS: Retrospective study of CRC patients who underwent preoperative 18 FDG-PET/CT and CT staging scans in a single referral center. The agreement between 18 FDG-PET/CT, contrast-enhanced CT, and colonoscopy for the surgical location was compared using the κ coefficient. Maximum standardized uptake (SUVmax ) value was obtained. Univariate and multivariate analyses were conducted. RESULTS: One hundred ninety-five patients were included. 18 FDG-PET/CT improved tumor localization in 84.6% (165/195) of cases (κ value 0.798, p < 0.001), thus correcting endoscopic errors 69.7% (30/43) of the time. In patients with incomplete colonoscopies, 18 FDG-PET/CT detected synchronous tumors in 2.5% (5/195) patients, overlooked by CT staging scans. Based on extracolonic 18 FDG-uptake, the second primary malignancy was diagnosed in 7(3.6%,7/195) patients and total accuracy for lymph node and distant metastasis was 66.1% and 98.4%, respectively. The treatment plan was altered in 30 (15.4%, 30/196) patients. There was a significant association between the SUVmax and tumor size (odds ratio [OR] 4.254, p = 0.003) and the depth of tumor invasion (OR 1.696, p = 0.026). CONCLUSIONS: Based on its ability to aid in preoperative evaluation and definitively alter surgical treatment planning, 18 FDG-PET/CT should be further evaluated in primary CRC.

Different Impact of Suspended Al2O3 Nanoparticles on Microbial Communities: Formation of 2D-Networks (Without Humic Acids) or 3D-Colonies (With Humic Acids).

The use of metal-based and, particularly, Al2O3 nanoparticles (Al2O3-NP) for diverse purposes is exponentially growing. However, the growth of such promissory market is not accompanied by a parallel extensive investigation related to the impact of this pollution on groundwater and biological systems. Pseudomonas species, ubiquitous, environmentally critical microbes, frequently respond to stress conditions with diverse strategies that generally include extracellular polymeric substances (EPS) formation. The aim of this study is to report that changes in the aqueous environment, particularly, the addition of Al2O3-NP without and with humic acids, induce different adaptive strategies of Pseudomonas aeruginosa early biofilms. To this purpose, early biofilms were incubated in diluted culture media without (control) and with Al2O3-NP, and with humic acids (HA-control, HA-Al2O3-NP) for 24 h. 3D colonies with EPS strings and isolated bacteria in their surroundings were detected in the control biofilms. Unlikely, an unusual adaptive behaviour was developed in the presence of Al2O3-NP. Bacteria opt to disassemble the 3D arrangements and to implement a 2D network promoting morphological and size changes of bacterial cells (small coccoid shapes). Remarkably, this strategy allows their temporarily non-EPS-depending survival without decreasing the number of cells. This behaviour was not observed with ZnO-NP, HA-Al2O3-NP, or HA-ZnO-NP. Physicochemical analysis revealed that HA were adsorbed on Al2O3-NP and promoted the Al(III) ions complexation. This supports the hypothesis that the reduction of toxicity of Al ions and the 3D colony formation in the presence of HA-Al2O3-NP is promoted by the complexation of the metal ions with HA components.

Perceived Emotional Impact of COVID-19 and Depressive Symptoms among Male Same-Sex Chilean Couples: Direct and Indirect Dyadic Associations through Relationship Satisfaction.

Stressors arising from the COVID-19 pandemic can spill over into the quality of couple relationships, with negative consequences on mental health. The mental health impact of COVID-19 might be particularly pronounced in disadvantaged populations such as LGBT people. This study aimed to examine direct and indirect dyadic associations between emotional impact of COVID-19 and depressive symptoms through relationship satisfaction in male same-sex couples. Using a cross-sectional design, 158 male same-sex Chilean couples completed self-report measures of the emotional impact of COVID-19, relationship satisfaction and depressive symptoms. We used the actor-partner interdependence mediation model for indistinguishable dyads to explore the direct and indirect dyadic associations. Results indicated that each partner's perceived emotional impact of COVID-19 was associated with his own higher depressive symptoms directly and indirectly, through his own lower relationship satisfaction. The other partner's perceived emotional impact of COVID-19 was associated with one's own higher depressive symptoms only directly. Our findings reinforce the notion that satisfactory couple relationships can act as a protective factor against depression in the LGBT population. Programs to promote adaptive coping strategies to deal with the emotional impact of the COVID-19 pandemic may have beneficial effects for the emotional adjustment of male same-sex couples, also by promoting relationship satisfaction.

Trichoderma as a biological control agent: mechanisms of action, benefits for crops and development of formulations.

Currently, the food and economic losses generated by the attack of phytopathogens on the agricultural sector constitute a severe problem. Conventional crop protection techniques based on the application of synthetic pesticides to combat these undesirable microorganisms have also begun to represent an inconvenience since the excessive use of these substances is associated with contamination problems and severe damage to the health of farmers, consumers, and communities surrounding the fields, as well as the generation of resistance by the phytopathogens to be combated. Using biocontrol agents such as Trichoderma to mitigate the attack of phytopathogens represents an alternative to synthetic pesticides, safe for health and the environment. This work explains the mechanisms of action through which Trichoderma exerts biological control, some of the beneficial aspects that it confers to the development of crops through its symbiotic interaction with plants, and the bioremedial effects that it presents in fields contaminated by synthetic pesticides. Also, detail the production of spore-based biopesticides through fermentation processes and formulation development.

Medicinal plants used by rural communities in the arid zone of Viesca and Parras Coahuila in northeast Mexico.

This study is the first record of medicinal plants in the southwest of the Coahuila state, an arid zone where extreme dry conditions prevail. One hundred twenty-two residents (in sixteen communities) were interviewed. The residents were questioned with a questionnaire-guided ethnomedical survey protocol about the various plants used. Seventy-seven species of medicinal plants belonging to 36 botanical families were cited. The highest use-value (UV) was calculated for Lippia graveolens Kunth (0.30); Aloe vera (L.) Burm.f. (0.20); Eucalyptus abdita Brooker & Hopper, Chamaemelum nobile (L.) All. (0.16); Mentha spicata L. (0.15) and Salvia officinalis L. (0.10). Informant consensus factor (ICF) about usages of medicinal plants ranges from 0.41 to 0.80; the highest level of agreement was determined between the informants and Respiratory System Diseases (0.80). The highest fidelity level (FL) values (100%) were identified in Flourensia cernua DC., Artisia ludoviciana Nutt., and Parthenium incanum Kunth to Gastro-intestinal System Diseases; Eucalyptus abdita Brooker & Hopper, Bougainvillea berberidifolia Heimerl, and Lippia graveolens Kunth to Respiratory System Diseases (RSD) and Cyclolepis genistoides D.Don and Ephedra antisyphilitica Berland. ex C.A.Mey. to Obstetrics, Gynecology and Urinary tract Diseases. These last two medicinal plant species ("palo azul" and "pitoreal") used by the rural communities in Viesca in the treatment of urinary tract infections and kidney stones have not been reported previously. These findings can provide new research directions for further phytochemical studies. The present study revealed that the residents are rich in ethno-medicinal knowledge and actively use medicinal plants to treat various diseases. New phytochemical and pharmacological research are needed to confirm the therapeutic potential and safety of the identified plants.

The negative effects of internalized homonegativity on sexual satisfaction: dyadic effects and gender-based differences in Chile.

Heterosexism is not only expressed through sexual prejudice as an external stressor, but also as an internalized rejection toward one's own (and others') sexually diverse identity. That is, lesbian women and gay men themselves internalize negative societal attitudes toward their sexual orientation and identity-a phenomenon called internalized homonegativity. A wealth of research shows that internalized homonegativity negatively affects the health and social adjustment of gay and lesbian people. However, the literature has documented this trend from an individual (over a dyadic) perspective, and largely among gay (over lesbian) samples. To address this oversight, we analyzed data from 210 gay and lesbian couples in Chile to examine both actor and partner effects of internalized homonegativity on their sexual satisfaction. Results from moderation analyses from an actor-partner interdependence model (APIM) approach show that partners' internalized homonegativity negatively affects actor sexual satisfaction, a pattern significantly moderated by gender; that is, only observed among lesbian couples. Our results further demonstrated that these effects hold above and beyond the actor and partner effects of age and relationship satisfaction, as well as relationship length. These results are consistent with the broader literature, which discusses the specific features of internalized homonegativity in lesbian women, characterized-among other aspects-by restrictive social demands over their sexuality. Accordingly, our findings highlight the deleterious relational consequences of internalized homonegativity and offer a relevant empirical contribution to the understanding of specific minority stress dynamics among lesbian women.

Optimization of human platelet lysate production and pathogen reduction in a public blood transfusion center.

BACKGROUND: Human platelet lysate (HPL) has been proposed as a safe and efficient xeno-free alternative to fetal bovine serum (FBS) for large-scale culturing of cell-based medicinal products. However, the use of blood derivatives poses a potential risk of pathogen transmission. To mitigate this risk, different pathogen reduction treatment (PRT) practices can be applied on starting materials or on final products, but these methods might modify the final composition and the quality of the products. STUDY DESIGN AND METHODS: We evaluated the impact of applying a PRT based on riboflavin and ultraviolet irradiation on the raw materials used to manufacture an improved Good Manufacturing Practices (GMP)-grade HPL product in a public blood center. Growth promotion and the levels of growth factors and proteins were compared between an inactivated product (HPL4-i) and a non-inactivated product (HPL4). Stability studies were performed at 4°C, -20°C, and -80°C. RESULTS: The application of a PRT on the starting materials significantly altered the protein composition of HPL4-i as compared with HPL4. Despite this, the growth promoting rates were unaffected when compared with FBS used as a control. While all products were stable at -20°C and -80°C for 24 months, a significant decrease in the activity of HPL4-i was observed when stored at 4°C. CONCLUSION: Our results show that the application of a PRT based on riboflavin and ultraviolet light on starting materials used in the manufacture of HPL modifies the final composition of the product, yet its cell growth promoting activity is maintained at levels similar to those of non-inactivated products.

Sorghum (Sorghum bicolor L.) as a potential source of bioactive substances and their biological properties.

Sorghum is the fifth cereal most produced in the world after wheat, rice, maize, and barley. In some regions, this crop is replacing maize, due to its high yield, resistance to drought and heat. There are several varieties of sorghum, whose coloration varies from cream, lemon-yellow, red, and even black. Pigmented sorghum grain is a rich source of antioxidants like polyphenols, mainly tannins, which have multiple benefits on human health such as, antiproliferative properties associated with the prevention of certain cancers, antioxidant activities related to the prevention of associated diseases to oxidative stress, antimicrobial and anti-inflammatory effects, it also improves glucose metabolism. Despite having these types of compounds, it is not possible to assimilate them, their use in the food industry has been limited, since sorghum is considered a food of low nutritional value, due to the presence of anti-nutritional factors such as strong tannins which form complexes with proteins and iron, thus reducing their digestibility. Based on these restrictions that this product has had as food for humans, the analysis of this review emphasizes the valorization of sorghum as a source of bioactive substances and the importance they confer on human health because of the biological potential it has.

Characteristics of migraine in patients with headache disorders: A clinic-based study from Central American and Caribbean countries.

OBJECTIVE: The objective of the study was to measure the proportion of patients who consulted for headache and of those who had a final diagnosis of migraine. We also assessed the proportion and characteristics of patients with migraine and the impact of migraine on the daily activities and the professional and social lives of patients visiting private/public medical centers in Guatemala, Costa Rica, Panama, and the Dominican Republic. BACKGROUND: Underdiagnosis of migraine is high in Central America and Caribbean urban communities. However, there is limited knowledge on characteristics of headache disorders for the appropriate classification of migraine, which is a prerequisite for targeted treatment. Hence, there is a need to improve migraine awareness among patients and medical professionals in this region. METHODS: Central America and Caribbean countries epidemioLogy study of Migraine (CALM) was a non-interventional, cross-sectional, multinational study in adults aged 18-65 years with a history of or current headache. The primary outcome was the proportion of patients with migraine visiting medical centers due to headache disorders. Using a specially designed migraine survey questionnaire, patients self-reported migraine characteristics, duration, and severity of attacks and impact on work and social life. RESULTS: Of the 313 enrolled patients, 308 (98.4%) completed the study. Approximately 75.3% (232/308) of patients with headache visiting medical centers had migraine, with episodic migraine being the most common (193 [83.2%]). Overall, 34/308 (11.0%) patients had a new diagnosis of migraine. Among patients with migraine, 66 (28.4%) had a history of migraine for ≥20 years and 59 (25.4%) experienced severe pain. Overall, 52.2% (121/232) of patients reported that migraine affected their professional life and 78.4% (182/232) reported an impact on social life. CONCLUSION: The CALM study establishes that a high proportion of patients with migraine had a long duration and high severity of migraine attacks, leading to a direct impact on work/social life as well as on costs incurred by patients in these countries.

A proprietary GMP human platelet lysate for the expansion of dermal fibroblasts for clinical applications.

Recent years have witnessed the introduction of ex vivo expanded dermal fibroblasts for several cell therapy and tissue-engineering applications, including the treatment of facial scars and burns, representing a promising cell type for regenerative medicine. We tested different in-house produced human platelet lysate (HPL) solutions against fetal bovine serum as supplements for in vitro fibroblast expansion by comparing cell yield, molecular marker expression, extracellular matrix (ECM) generation, genomic stability and global gene expression. Our in-house produced HPL supported fibroblast growth at levels similar to those for FBS and commercial HPL products and was superior to AB human serum. Cells grown in HPL maintained a fibroblast phenotype (VIM+, CD44+, CD13+, CD90+), ECM generation capacity (FN+, COL1+) and a normal karyotype, although gene expression profiling revealed changes related to cell metabolism, adhesion and cellular senescence. The HPL manufacturing process was validated within a GMP compliant system and the solution was stable at -80ºC and -20ºC for 2 years. Dermal fibroblasts expanded in vitro with HPL maintain a normal karyotype and expression of fibroblast markers, with only minor changes in their global gene expression profile. Our in-house produced GMP-HPL is an efficient, safe and economical cell culture supplement that can help increase the healthcare activity of blood transfusion centers through the re-use of transfusional plasma and platelets approaching their expiration date. Currently, our HPL solution is approved by the Spanish Agency of Medicines and Medical Devices and is being used in the manufacture of cell therapy products.Abbreviations: AB plasma: plasma group AB; ABHS: AB Human Serum; ABHS+GF: AB Human Serum supplemented with growth factors; ANOVA: Analysis of variance; ATMPs: Advanced Therapies for Medicinal Products; CPE: cytopathic effect; DEGs: Differentially expressed genes; DMEM: Dulbecco's modified Eagle's Medium; ECM: Extracellular matrix; ELISA: enzyme-linked immunosorbent assay; FBS: Fetal bovine serum; FDR: False discovery rate; FGF: Fibroblast growth factor; GMP: Good manufacturing practice; HPL: Human platelet lysate; HPL-CM: commercial human platelet lysate; MSCs: mesenchymal stem cells; NEAA: non-essential amino acids; P/S: penicillin/streptomycin; PBS: phosphate buffered saline; PC: leukodepleted platelet concentrate; PCR: polymerase chain reaction; PDGF: Platelet-derived growth factor; PDGFRA: Platelet-derived growth factor receptor alpha; qPCR: quantitative polymerase chain reaction; RNA: Ribonucleic acid; RT: Room temperature; TAC: Transcriptome analysis console; TGF-ß: Transforming growth factor beta.

Prediction of insulin therapy in women with gestational diabetes: a systematic review and meta-analysis of observational studies.

OBJECTIVES: To identify antenatal risk factors that may predict the need for insulin treatment upon diagnosis of gestational diabetes (GDM), that is, to identify the specific characteristics of women diagnosed with GDM who did not achieve good glycemic control through lifestyle modifications. METHODS: We performed a comprehensive literature search in PubMed, Science Direct, Ebsco, and Scielo for studies evaluating the associations between antenatal factors and the need for insulin treatment published until January 28th, 2021. Random-effects models were used to estimate risk ratios and their 95% confidence interval. The quality of studies was assessed using the Newcastle-Ottawa Scale. Random-effects models were used to estimate outcomes, and effects reported as risk ratio and their 95% confidence interval. The systematic review and meta-analysis were registered in the International Prospective Register of Systematic Reviews. RESULTS: Eighteen observational studies were selected, reporting 14,951 women with GDM of whom 5,371 received insulin treatment. There were statistically significant associations between the need for insulin treatment and BMI ≥ 30 (RR:2.2; 95%CI: 1.44-3.41), family history of type 2 diabetes mellitus (RR:1.74; 95%CI: 1.56-1.93), prior personal history of GDM (RR:2.10; 95%CI: 1.56-2.82), glycated hemoglobin value at GDM diagnosis (RR:2.12; 95%CI: 1.77-2.54), and basal glycemia obtained in the diagnostic curve (RR: 1.2; 95%CI: 1.12-1.28). Nulliparity and maternal age were not determinants factor. There was moderate-to-high heterogeneity among the included studies. CONCLUSIONS: the strong causal association between BMI ≥ 30, family history of type 2 diabetes mellitus, prior history of GDM and glycosylated hemoglobin with the need for insulin treatment was revealed.

Pregnancy-Associated Diabetes Mellitus and Stillbirths by Race and Ethnicity among Hospitalized Pregnant Women in the United States.

OBJECTIVES: Racial disparities in preexisting diabetes mellitus (PDM) and gestational diabetes mellitus (GDM) remain largely unexplored. We examined national PDM and GDM prevalence trends by race/ethnicity and the association between these conditions and fetal death. METHODS: This was a retrospective cross-sectional analysis of 69,539,875 pregnancy-related hospitalizations from 2002 to 2017 including 674,040 women with PDM (1.0%) and 2,960,797 (4.3%) with GDM from the US Nationwide Inpatient Sample Survey. Joinpoint regression was used to evaluate trends in prevalence. Survey logistic regression was used to evaluate the association between exposures (PDM and GDM) and outcome. RESULTS: Overall, the average annual increase in prevalence was 5.2% (95% confidence interval [CI] 4.2-6.2) for GDM and 1.0% (95% CI -0.1 to 2.0) for PDM, during the study period. Hispanic (average annual percentage change 5.3, 95% CI 3.6 - 7.1) and non-Hispanic Black (average annual percentage change 0.9, 95% CI 0.1 - 1.7) women had the highest average annual percentage increase in the prevalence of GDM and PDM, respectively. After adjustment, the odds of stillbirth were highest for Hispanic women with PDM (odds ratio 2.41, 95% CI 2.23-2.60) and decreased for women with GDM (odds ratio 0.51, 95% CI 0.50-0.53), irrespective of race/ethnicity. CONCLUSIONS: PDM and GDM prevalence is increasing in the United States, with the highest average annual percentage changes seen among minority women. Furthermore, the reasons for the variation in the occurrence of stillbirths among mothers with PDM and GDM by race/ethnicity are not clear and warrant additional research.

Synthesis, In Silico, and Biological Evaluation of a Borinic Tryptophan-Derivative That Induces Melatonin-like Amelioration of Cognitive Deficit in Male Rat.

Preclinical and clinical evidence supports melatonin and its analogues as potential treatment for diseases involving cognitive deficit such as Alzheimer's disease. In this work, we evaluated by in silico studies a set of boron-containing melatonin analogues on MT1 and MT2 receptors. Then, we synthesized a compound (borolatonin) identified as potent agonist. After chemical characterization, its evaluation in a rat model with cognitive deficit showed that it induced ameliorative effects such as those induced by equimolar administration of melatonin in behavioral tests and in neuronal immunohistochemistry assays. Our results suggest the observed effects are by means of action on the melatonin system. Further studies are required to clarify the mechanism(s) of action, as the beneficial effects on disturbed memory by gonadectomy in male rats are attractive.

Mexican Oregano (Lippia berlandieri Schauer and Poliomintha longiflora Gray) Essential Oils Induce Cell Death by Apoptosis in Leishmania (Leishmania) mexicana Promastigotes.

Leishmaniasis is a neglected vector-borne disease; there are different manifestations of the diseases and species involved, and cutaneous leishmaniasis caused by Leishmania (L.) mexicana is the most prevalent in Mexico. Currently, the drugs available for the treatment of leishmaniasis are toxic, expensive, and often ineffective; therefore, it is imperative to carry out research and development of new therapeutic alternatives, with natural products being an attractive option. In particular, oregano is a plant with worldwide distribution; in Mexico, two species: Lippia berlandieri Schauer and Poliomintha longiflora Gray are endemic. Both essential oils (EO's) have been reported to have antimicrobial activity attributed to their main components, thymol and carvacrol. In this research, the leishmanicidal effect and mechanism of cell death induced by L. berlandieri EO, P. longiflora EO, thymol, and carvacrol in L. mexicana promastigotes were determined in vitro. Additionally, the cytotoxic activity in mammalian cells was evaluated. L. berlandieri EO presented higher leishmanicidal activity (IC50 = 41.78 µg/mL) than P. longiflora EO (IC50 = 77.90 µg/mL). Thymol and carvacrol were the major components of both Mexican oregano EO's. Thymol presented higher leishmanial inhibitory activity (IC50 = 22.39 µg/mL), above that of carvacrol (IC50 = 61.52 µg/mL). All the EO's and compounds evaluated presented lower cytotoxic activity than the reference drug; thymol was the compound with the best selectivity index (SI). In all cases, apoptosis was identified as the main mechanism of death induced in the parasites. The leishmanicidal capacity of the Mexican oregano EO is an accessible and affordable alternative that can be further explored.

Acute emphysematous cholecystitis due to clostridium perfringens: a rare entity requiring aggressive and early treatment.

Acute emphysematous cholecystitis is a rare entity (1% of acute cholecystitis) characterized by the presence of gas in the gallbladder lumen, gallbladder wall or even in the bile duct (pneumobilia). It is associated with arteriosclerosis, embolic events, and diabetes mellitus and as in other similar pathologies such as emphysematous gastritis or emphysematous pancreatitis the most frequently isolated microorganisms are Streptococcus pyogenes, Escherichia coli and Staphylococcus aureus, although others such as Proteus vulgaris, Pseudomonas aeruginosa, Clostridium perfringens and Klebsiella pneumoniae have also been found.

Voltage Imaging with a NIR-Absorbing Phosphine Oxide Rhodamine Voltage Reporter.

The development of fluorescent dyes that emit and absorb light at wavelengths greater than 700 nm and that respond to biochemical and biophysical events in living systems remains an outstanding challenge for noninvasive optical imaging. Here, we report the design, synthesis, and application of near-infrared (NIR)-absorbing and -emitting optical voltmeter based on a sulfonated, phosphine-oxide (po) rhodamine for voltage imaging in intact retinas. We find that po-rhodamine based voltage reporters, or poRhoVRs, display NIR excitation and emission profiles at greater than 700 nm, show a range of voltage sensitivities (13 to 43% ΔF/F per 100 mV in HEK cells), and can be combined with existing optical sensors, like Ca2+-sensitive fluorescent proteins (GCaMP), and actuators, like light-activated opsins ChannelRhodopsin-2 (ChR2). Simultaneous voltage and Ca2+ imaging reveals differences in activity dynamics in rat hippocampal neurons, and pairing poRhoVR with blue-light based ChR2 affords all-optical electrophysiology. In ex vivo retinas isolated from a mouse model of retinal degeneration, poRhoVR, together with GCaMP-based Ca2+ imaging and traditional multielectrode array (MEA) recording, can provide a comprehensive physiological activity profile of neuronal activity, revealing differences in voltage and Ca2+ dynamics within hyperactive networks of the mouse retina. Taken together, these experiments establish that poRhoVR will open new horizons in optical interrogation of cellular and neuronal physiology in intact systems.

No evidence for a difference in 2D:4D ratio between youth with elevated prenatal androgen exposure due to congenital adrenal hyperplasia and controls.

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: ß = -0.001 (-0.008, 0.006); females: ß = -0.004 [-0.015, 0.007]; males: ß = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.