Protocell Flow Reactors for Enzyme and Whole-Cell Mediated Biocatalysis.

The design and construction of continuous flow biochemical reactors comprising immobilized biocatalysts have generated great interest in the efficient synthesis of value-added chemicals. Living cells use compartmentalization and reaction-diffusion processes for spatiotemporal regulation of biocatalytic reactions, and implementing these strategies into continuous flow reactors can offer new opportunities in reactor design and application. Herein, the fabrication of protocell-based continuous flow reactors for enzyme and whole-cell mediated biocatalysis is demonstrated. Semipermeable membranized coacervate vesicles are employed as model protocells that spontaneously sequester enzymes or accumulate living bacteria to produce embodied microreactors capable of single- or multiple-step catalytic reactions. By packing millions of the enzyme/bacteria-containing coacervate vesicles in a glass column, a facile, cost-effective, and modular methodology capable of performing oxidoreductase, peroxidase and lipolytic reactions, enzyme-mediated L-DOPA synthesis, and whole-cell glycolysis under continuous flow conditions, is demonstrated. It is shown that the protocell-nested enzymes and bacterial cells exhibit enhanced activities and stability under deleterious operating conditions compared with their non-encapsulated counterparts. These results provide a step toward the engineering of continuous flow reactors based on cell-like microscale agents and offer opportunities in the development of green and sustainable industrial bioprocessing.

Enhancing the sequence coverage of nanodiamond-extracted early secretory proteins from the Mycobacterium tuberculosis complex.

The unambiguous identification of protein species requires high sequence coverage. In this study, we successfully improved the sequence coverage of early secretory 10 kDa cell filtrate protein (CFP-10) and 6 kDa early secretory antigenic target (ESAT-6) proteins from the Mycobacterium tuberculosis complex (MTC) in broth culture media with the use of the 4-chloro-α-cyanocinnamic acid (Cl-CCA) matrix. Conventional matrices, α-cyano-hydroxy-cinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB), were also used for comparison. After nanodiamond (ND) extraction, the sequence coverage of the CFP-10 protein was 87% when CHCA and DHB matrices were used, and the ESAT-6 protein was not detected. On the other hand, the sequence coverage for ND-extracted CFP-10 and ESAT-6 could reach 94% and 100%, respectively, when the Cl-CCA matrix was used and with the removal of interference from bovine serum albumin (BSA) protein and α-crystallin (ACR) protein. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was also adopted to analyze the protein mass spectra. A total of 6 prominent ion signals were observed, including ESAT-6 protein peaks at mass-to-charge ratios (m/z) of ∼7931, ∼7974, ∼9768, and ∼9813 and CFP-10 protein peaks at m/z of ∼10 100 and ∼10 660. The ESAT-6 ion signals were always detected concurrently with CFP-10 ion signals, but CFP-10 ion signals could be detected alone without the ESAT-6 ion signals. Furthermore, the newly found ESAT-6 peaks were also confirmed using a Mag-Beads-Protein G kit with an ESAT-6 antibody to capture the ESAT-6 protein, which was also consistent with the sequence coverage analysis.

Detonation of fulminating gold produces heterogeneous gold nanoparticles.

Fulminating gold, the first high-explosive compound to be discovered, disintegrates into a mysterious cloud of purple smoke, the nature of which has been speculated upon since its discovery in the 15th century. In this work, we show that the colour of the smoke is due to the presence of gold nanoparticles.

A Critical Review on Detection of Foodborne Pathogens Using Electrochemical Biosensors.

An outbreak of foodborne pathogens would cause severe consequences. Detecting and diagnosing foodborne diseases is crucial for food safety, and it is increasingly important to develop fast, sensitive, and cost-effective methods for detecting foodborne pathogens. In contrast to traditional methods, such as medium-based culture, nucleic acid amplification test, and enzyme-linked immunosorbent assay, electrochemical biosensors possess the advantages of simplicity, rapidity, high sensitivity, miniaturization, and low cost, making them ideal for developing pathogen-sensing devices. The biorecognition layer, consisting of recognition elements, such as aptamers, antibodies and bacteriophages, and other biomolecules or polymers, is the most critical component to determine the selectivity, specificity, reproducibility, and lifetime of a biosensor when detecting pathogens in a biosample. Furthermore, nanomaterials have been frequently used to improve electrochemical biosensors for sensitively detecting foodborne pathogens due to their high conductivity, surface-to-volume ratio, and electrocatalytic activity. In this review, we survey the characteristics of biorecognition elements and nanomaterials in constructing electrochemical biosensors applicable for detecting foodborne pathogens during the past five years. As well as the challenges and opportunities of electrochemical biosensors in the application of foodborne pathogen detection are discussed.

Clinical implications of crown-rump length discordance at 11 to 14 weeks in dichorionic twins.

BACKGROUND: Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. OBJECTIVE: This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. STUDY DESIGN: This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. RESULTS: Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. CONCLUSION: Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.

Development of a linear ion trap mass spectrometer capable of analyzing megadalton MALDI ions.

Detecting megadalton matrix-assisted laser desorption/ionization (MALDI) ions in an ion trap mass spectrometer is a technical challenge. In this study, megadalton protein and polymer ions were successfully measured by MALDI linear ion trap mass spectrometer (LIT-MS) for the first time. The LIT-MS is comprised of a Thermo linear ion trap mass analyzer and a highly sensitive charge-sensing particle detector (CSPD). A newly designed radio frequency (rf) scan mode with dipolar resonance ejection techniques is proposed to extend the mass range of LIT-MS up to one million Thomson (Th). We analyze high mass ions with mass-to charge (m/z) ratios ranging from 100 kTh to 1 MTh, including thyroglobulin, alpha-2-macroglobulin, immunoglobulins (e.g., IgG and IgM), and polymer (∼ 940 kTh) ions. Besides, it is also very challenging for ion trap mass spectrometry to detect megadalton ions at low concentrations. By adopting high affinity carboxylated/oxidized detonation nanodiamonds (oxDNDs) to enrich IgM molecules and form antibody-nanodiamond conjugates, we have successfully reached âˆ¼ 5 nM (5 µg/mL) concentration which is better than that by the other techniques.

Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study.

BACKGROUND: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

Recent Advances in Electrochemical Immunosensors with Nanomaterial Assistance for Signal Amplification.

Electrochemical immunosensors have attracted immense attention due to the ease of mass electrode production and the high compatibility of the miniature electric reader, which is beneficial for developing point-of-care diagnostic devices. Electrochemical immunosensors can be divided into label-free and label-based sensing strategies equipped with potentiometric, amperometric, voltammetric, or impedimetric detectors. Emerging nanomaterials are frequently used on electrochemical immunosensors as a highly rough and conductive interface of the electrodes or on nanocarriers of immobilizing capture antibodies, electroactive mediators, or catalyzers. Adopting nanomaterials can increase immunosensor characteristics with lower detection limits and better sensitivity. Recent research has shown innovative immobilization procedures of nanomaterials which meet the requirements of different electrochemical immunosensors. This review discusses the past five years of advances in nanomaterials (metal nanoparticles, metal nanostructures, carbon nanotubes, and graphene) integrated into the electrochemical immunosensor. Furthermore, the new tendency and endeavors of nanomaterial-based electrochemical immunosensors are discussed.

TLR7 agonist RO7020531 versus placebo in healthy volunteers and patients with chronic hepatitis B virus infection: a randomised, observer-blind, placebo-controlled, phase 1 trial.

BACKGROUND: Toll-like receptor 7 (TLR7) agonists augment immune activity and have potential for the treatment of chronic hepatitis B virus (HBV) infection. We aimed to assess the safety and tolerability of RO7020531 (also called RG7854), a prodrug of the TLR7 agonist RO7011785, in healthy volunteers and patients with chronic HBV infection. METHODS: This randomised, observer-blind, placebo-controlled, phase 1 study was done in two parts. Part 1 was done at one site in New Zealand and part 2 was done at 12 sites in Bulgaria, Hong Kong, Italy, New Zealand, the Netherlands, Taiwan, Thailand, and the UK. In part 1, healthy volunteers were randomly assigned (4:1) within one of eight dose cohorts (3 mg, 10 mg, 20 mg, 40 mg, 60 mg, 100 mg, 140 mg, or 170 mg) to receive a single RO7020531 dose or placebo or randomly assigned (4:1) within one of three dose cohorts (100 mg, 140 mg, or 170 mg) to receive either RO7020531 or placebo every other day for 13 days. In part 2, nucleoside or nucleotide analogue-suppressed patients with chronic HBV infection were randomly assigned (4:1) within cohorts 1-3 (150 mg, 150 mg, or 170 mg) to receive either RO7020531 or placebo and treatment-naive patients with chronic HBV infection were randomly assigned (3:1) in cohort 4 to receive either 150 mg of RO7020531 or placebo. Patients were treated every other day for 6 weeks. Study medication was administered orally to participants after they had fasted. Study participants and investigational staff were masked to treatment allocation. The primary outcome was the safety and tolerability of RO7020531, as measured by the incidence and severity of adverse events and the incidence of laboratory, vital sign, and electrocardiogram abnormalities, and was analysed in all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT02956850, and the study is complete. FINDINGS: Between Dec 12, 2016, and March 21, 2021, 340 healthy volunteers were screened in part 1, of whom 80 were randomly assigned in the single ascending dose study (eight assigned RO7020531 in each cohort and 16 assigned placebo) and 30 were randomly assigned in the multiple ascending dose study (eight assigned RO7020531 in each cohort and six assigned placebo), and 110 patients were screened in part 2, of whom 30 were randomly assigned in cohorts 1-3 (16 assigned RO7020531 150 mg, eight assigned RO7020531 170 mg, and six assigned placebo) and 20 were randomly assigned in cohort 4 (15 assigned RO7020531 and five assigned placebo). All randomly assigned participants received at least one dose of a study drug and were included in the safety analysis. All tested doses of RO7020531 were safe and had acceptable tolerability in healthy volunteers and patients. The most frequent treatment-related adverse events among the total study population were headache (15 [9%] of 160 participants), influenza-like illness (seven [4%] of 160 participants), and pyrexia (ten [6%] of 160 participants). Most adverse events were mild and transient. There were no severe or serious adverse events in healthy volunteers. In the patient cohorts, there was one severe adverse event (influenza-like illness with 170 mg of RO7020531) and one serious adverse event (moderate influenza-like illness with a 3-day hospitalisation in a treatment-naive patient receiving RO7020531). There were no treatment-related deaths. INTERPRETATION: Due to acceptable safety and tolerability, RO7020531 should continue to be developed for the treatment of patients with chronic HBV infection. FUNDING: F Hoffmann-La Roche.

Mediators of energy homeostasis in hyperthyroidism

ABSTRACT Objective: The aim of this study was to assess the effect of hyperthyroidism and its treatment on body weight and composition, insulin resistance, and mediators of appetite and energy homeostasis, namely ghrelin, leptin, adiponectin, and fibroblast growth factor 21 (FGF21). Subjects and methods: Thirty-five adult patients (27 female and 8 male, aged 39.63 ± 9.70 years) with overt hyperthyroidism were evaluated for leptin, ghrelin, adiponectin, and FGF21 levels; insulin resistance; and body composition using DEXA both at baseline and a minimum of two months following normalization of serum thyroxin on carbimazole treatment. Comparison of means between the baseline and post treatment values was performed by the paired t test for normally distributed parameters and by the Wilcoxon signed-rank test for non-normally distributed data. Results: Hyperthyroidism correction resulted in an increase in weight from 51.15 ± 8.50 kg to 55.74 ± 8.74 kg (P < 0.001), paradoxically accompanied by a decrease in insulin resistance as measured by HOMA-IR from 1.35 (1.02-1.72) to 0.73 (0.52-0.93) ( P < 0.001). Correction of hyperthyroidism was also associated with a decrease in FGF21 from 58 (55-64) to 52 (47-58) pg/mL ( P < 0.001) and in leptin levels from 17 (7-36) to 11 (4.6-28) ng/mL ( P = 0.03). Conclusion: Despite lower body weight, thyrotoxicosis is associated with insulin resistance. High levels of thermogenic hormones, leptin, and FGF21 were observed in thyrotoxicosis and may be partly responsible for the excessive heat production typical of this condition.

Mediators of energy homeostasis in hyperthyroidism.

Objective: The aim of this study was to assess the effect of hyperthyroidism and its treatment on body weight and composition, insulin resistance, and mediators of appetite and energy homeostasis, namely ghrelin, leptin, adiponectin, and fibroblast growth factor 21 (FGF21). Subjects and methods: Thirty-five adult patients (27 female and 8 male, aged 39.63 ± 9.70 years) with overt hyperthyroidism were evaluated for leptin, ghrelin, adiponectin, and FGF21 levels; insulin resistance; and body composition using DEXA both at baseline and a minimum of two months following normalization of serum thyroxin on carbimazole treatment. Comparison of means between the baseline and post treatment values was performed by the paired t test for normally distributed parameters and by the Wilcoxon signed-rank test for non-normally distributed data. Results: Hyperthyroidism correction resulted in an increase in weight from 51.15 ± 8.50 kg to 55.74 ± 8.74 kg (P < 0.001), paradoxically accompanied by a decrease in insulin resistance as measured by HOMA-IR from 1.35 (1.02-1.72) to 0.73 (0.52-0.93) (P < 0.001). Correction of hyperthyroidism was also associated with a decrease in FGF21 from 58 (55-64) to 52 (47-58) pg/mL (P < 0.001) and in leptin levels from 17 (7-36) to 11 (4.6-28) ng/mL (P = 0.03). Conclusion: Despite lower body weight, thyrotoxicosis is associated with insulin resistance. High levels of thermogenic hormones, leptin, and FGF21 were observed in thyrotoxicosis and may be partly responsible for the excessive heat production typical of this condition.

Telehealth multidisciplinary prenatal consultation during the COVID-19 pandemic: enhancing patient care coordination while maintaining high provider satisfaction.

OBJECTIVE: Comprehensive fetal care centers address congenital anomalies by developing pre- and post-natal care plans in a multidisciplinary format. To reduce exposure during the Coronavirus Infectious Disease-2019 (COVID-19) pandemic, the Centers for Medicare & Medicaid Services (CMS) broadened access to telehealth services. We assessed provider satisfaction with the rapid transition from in-person prenatal visits to multidisciplinary consultations via telehealth as an adaptive response to the pandemic. METHODS: Patients referred to an urban academic fetal care center during the first 6 weeks of the COVID-19 pandemic underwent advanced imaging including fetal MRI, focused ultrasound, and fetal echocardiography. Subsequently, multidisciplinary telehealth consultations occurred with all providers attending virtually. Patients were given the option of attending the multidisciplinary telehealth consultation in a conference room in the hospital or from home. During these meetings, relevant images were reviewed with all participants via screen sharing through a secure video platform. Provider satisfaction with the telehealth paradigm was assessed using an electronic survey. RESULTS: Twenty-two surveys were administered with a response rate of 82%. 89% of providers were highly satisfied with the telehealth format. 72% of providers would prefer the multidisciplinary telehealth format to an in-person visit for future visits after COVID-19 restrictions are lifted. 22% of providers would leave the choice to the patient's family. One provider preferred in-person visits. Some providers noted that virtual conferences limited the ability to draw pictures, show educational materials, and provide emotional support. CONCLUSION: Providers were overwhelmingly supportive of continuing multidisciplinary telehealth conferences for complex prenatal consultations, even after restrictions are lifted, which has led to the continuation of this model for the duration of the pandemic. Providers highlighted the convenience and improved care coordination across specialties. Further studies to examine the patient experience with virtual consultations are warranted.

Spontaneous Membranization in a Silk-Based Coacervate Protocell Model.

Molecularly crowded coacervate micro-droplets are useful protocell constructs but the absence of a physical membrane limits their application as cytomimetic models. Auxiliary surface-active agents have been harnessed to stabilize the coacervate droplets by irreversible shell formation but endogenous processes of reversible membranization have received minimal attention. Herein, we describe a dynamic alginate/silk coacervate-based protocell model in which membrane-less droplets are reversibly reconfigured and inflated into semipermeable coacervate vesicles by spontaneous self-organization of amphiphilic silk polymers at the droplet surface under non-neutral charge conditions in the absence of auxiliary agents. We show that membranization can be reversibly controlled endogenously by programming the pH within the protocells using an antagonistic enzyme system such that structural reconfigurations in the protocell microstructure are coupled to the trafficking of water-soluble solutes. Our results open new perspectives in the design of hybrid protocell models with dynamical structural properties.

Systematic review and meta-analysis of COVID-19 maternal and neonatal clinical features and pregnancy outcomes up to June 3, 2021.

OBJECTIVE: COVID-19 is a rapidly changing and developing emergency that requires constant re-evaluation of available data. We report a systematic review and meta-analysis based on all published high-quality data up to and including June 3, 2021 on the maternal and neonatal outcomes in pregnant women infected with COVID-19. DATA SOURCES: PubMed, SCOPUS, MEDLINE, ClinicalTrials.gov, and Web of Science databases were queried from inception up to June 3, 2021. STUDY ELIGIBILITY CRITERIA: We included all clinical studies (prospective and retrospective cohort studies, case-control studies, case series, and rapid communications) that reported data on any maternal and neonatal outcomes of pregnant women with COVID-19. METHODS: The data were analyzed as pooled proportions or odds ratios and 95% confidence intervals in meta-analysis models. RESULTS: We included 111 studies enrolling 42,754 COVID-19-positive pregnant women. From COVID-19-positive pregnant women, the incidence rates were 53.2% (95% confidence interval, 48-58.4) for cesarean delivery, 41.5% (95% confidence interval, 36.3-46.8) for spontaneous vaginal delivery, and 6.4% (95% confidence interval, 4.5-9.2) for operative delivery. The rates of some adverse neonatal events, including premature delivery (16.7%; 95% confidence interval, 12.8-21.5) and low birthweight (16.7%; 95% confidence interval, 12.8-21.5) were relatively high in mothers infected with COVID-19. Vertical transmission (3.5%; 95% confidence interval, 2.7-4.7), neonatal death (3%; 95% confidence interval, 2-4), stillbirth (1.9%; 95% confidence interval, 1.5-2.4), and maternal mortality (0.012%; 95% confidence interval, 0.010-0.014) were rare adverse events. The mean birthweight was 3069.7 g (95% confidence interval, 3009.7-3129.8 g). In the comparative analysis, COVID-19 significantly increased the risk of premature delivery (odds ratio, 1. 48 [95% confidence interval, 1.22-1.8]), preeclampsia (odds ratio, 1.6 [95% confidence interval, 1.2-2.1]), stillbirth (odds ratio, 2.36 [95% confidence interval, 1.24-4.462]), neonatal mortality (odds ratio, 3.35 [95% confidence interval, 1.07-10.5]), and maternal mortality (odds ratio, 3.08 [95% confidence interval, 1.5-6.3]). The pooled analyses were homogenous, with mild heterogeneity in premature delivery and preeclampsia outcomes. CONCLUSION: The data must be interpreted with caution as limited data are available, and no complete assessment of bias is possible at this time. Our data suggest that pregnant women who test positive for COVID-19 seem to be at a higher risk of lower birth weights and premature delivery. There is no evidence at this time of the sharply increased maternal mortality that was seen previously with both the 2003 SARS and 2012 MERS pandemics.

The Hassan Neonatal Morbidity Composite Scale and Neonatal Length of Stay-A Validation Study.

OBJECTIVE: Obstetric studies often report neonatal morbidity as a composite score. Composite scores can simplify data analysis when multiple outcomes of interest are present and allows researchers to conduct smaller, more manageable trials. The Hassan scale is a neonatal morbidity composite scale that assigns high scores to infants with multiple morbidities and low scores to infants without or with single morbidities. The objective of this study was to validate the association between scores on the Hassan scale and neonatal intensive care unit (NICU) length of stay STUDY DESIGN: We conducted a cohort study of all infants born between 22 and 366/7 weeks' gestation and cared for within 419 neonatal units in the Pediatrix Medical Group between 1997 and 2018. Each infant was assigned a Hassan's score based on the number of neonatal morbidity events that occurred during the delivery hospitalization. The association between Hassan's scores and neonatal length of stay was evaluated using linear regression. Multivariable models were constructed to determine if the Hassan score was independently associated with neonatal length of stay. RESULTS: There were 760,037 infants included. The median (interquartile range [IQR]) gestational age of delivery was 34 (31, 35) weeks and the median (IQR) birth weight at delivery was 2,000 (1,503, 2,430) g. The median length of stay for infants discharged home was 17 (10-33) days. A Hassan's score was able to be assigned to 699,206 (92%) patients. Neonatal morbidities included in the Hassan scale were more common among infants born earlier in gestation. On adjusted analysis, the Hassan scale was found to be independently associated with neonatal length of stay (p < 0.001, coefficient = 10.4 days [95% confidence interval (CI): 10.3, 10.4 days]) with higher scores associated with longer lengths of stay. CONCLUSION: The Hassan scale, more than a binary composite score, is able to differentiate preterm infants with prolonged hospitalizations from those with short hospitalizations. KEY POINTS: · The Hassan scale is an independent predictor of neonatal length of stay.. · Classification of infants based on number of morbidities correlates with neonatal length of stay.. · The Hassan scale provided better discrimination than binary composite morbidity scores.. · The Hassan scale may be an economic predictor of health-related costs..

Stimuli-Responsive Nucleotide-Amino Acid Hybrid Supramolecular Hydrogels.

The ability to assemble chemically different gelator molecules into complex supramolecular hydrogels provides excellent opportunities to construct functional soft materials. Herein, we demonstrate the formation of hybrid nucleotide-amino acid supramolecular hydrogels. These are generated by the silver ion (Ag+)-triggered formation of silver-guanosine monophosphate (GMP) dimers, which undergo self-assembly through non-covalent interactions to produce nanofilaments. This process results in a concomitant pH reduction due to the abstraction of a proton from the guanine residue, which triggers the in situ gelation of a pH-sensitive amino acid, N-fluorenylmethyloxycarbonyl tyrosine (FY), to form nucleotide-amino acid hybrid hydrogels. Alterations in the supramolecular structures due to changes in the assembly process are observed, with the molar ratio of Ag:GMP:FY affecting the assembly kinetics, and the resulting supramolecular organisation and mechanical properties of the hydrogels. Higher Ag:GMP stoichiometries result in almost instantaneous gelation with non-orthogonal assembly of the gelators, while at lower molar ratios, orthogonal assembly is observed. Significantly, by increasing the pH as an external stimulus, nanofilaments comprising FY can be selectively disassembled from the hybrid hydrogels. Our results demonstrate a simple approach for the construction of multicomponent stimuli-responsive supramolecular hydrogels with adaptable network and mechanical properties.

Chemical-mediated translocation in protocell-based microactuators.

Artificial cell-like communities participate in diverse modes of chemical interaction but exhibit minimal interfacing with their local environment. Here we develop an interactive microsystem based on the immobilization of a population of enzyme-active semipermeable proteinosomes within a helical hydrogel filament to implement signal-induced movement. We attach large single-polynucleotide/peptide microcapsules at one or both ends of the helical protocell filament to produce free-standing soft microactuators that sense and process chemical signals to perform mechanical work. Different modes of translocation are achieved by synergistic or antagonistic enzyme reactions located within the helical connector or inside the attached microcapsule loads. Mounting the microactuators on a ratchet-like surface produces a directional push-pull movement. Our methodology opens up a route to protocell-based chemical systems capable of utilizing mechanical work and provides a step towards the engineering of soft microscale objects with increased levels of operational autonomy.

Effect of Correction of Hyperthyroidism with Anti-thyroid Drugs on the Glycated Hemoglobin in Non-diabetic Patients with Primary Hyperthyroidism.

BACKGROUND: Glycated hemoglobin (HbA1c) levels are dependent not only on the average blood glucose levels over the preceding 2 - 3 months but also on the turnover of erythrocytes. Hyperthyroidism is known to be associated with an increase in erythrocyte turnover that may falsely lower the HbA1c in relation to the level of glycemia. OBJECTIVES: To assess the impact of medical correction of hyperthyroidism on HbA1c, independent of changes in the fasting plasma glucose and 2-hour post-oral glucose tolerance test plasma glucose. METHODS: Adult patients with overt hyperthyroidism (n = 36) were tested for their hemoglobin, reticulocyte percentage, HbA1c and fasting and post-oral glucose tolerance test (OGTT) 2-hour plasma glucose, both at baseline and following at least three months of near normalization of serum thyroxin on Carbimazole treatment. RESULTS: Correction of hyperthyroidism in 36 patients was associated with an increase in the hemoglobin (P = 0.004) and a rise in HbA1c (P = 0.025), even though no significant change was observed in both the fasting (P = 0.28) and post OGTT two-hour plasma glucose (P = 0.54). Also, the proportion of patients with HbA1c ≥ 5.7% rose from 3/36 to 10/36; P = 0.016, while the proportion of patients with either abnormal fasting or abnormal post OGTT 2-hour plasma glucose or both did not show any significant change (P = 0.5). The sensitivity of HbA1c to diagnose prediabetes increased from 20% to 50% post- treatment. CONCLUSIONS: Glycated hemoglobin is falsely low in relation to glycemia in patients with untreated hyperthyroidism.

Quality of life and mental health status of hansen disease patients, attending a designated leprosy care center in South-India.

Background: "Quality of life (QOL)" is relatively a new concept, which originates from the World Health Organization (WHO) "health" definition. The WHO defines "health" as a state of complete physical, mental, and social well-being and not merely an absence of disease or infirmity. It introduces a word, "well-being," which has two components, one the objective component and the second subjective component. The objective component mainly includes all the material possession by an individual, whereas the subjective component includes the perception of health by an individual, i.e., "QoL." It has been observed that most of the persons affected by Hansen's Disease (leprosy) have good economic conditions, but they continue to suffer from social, psychological, and physical problems which makes their life miserable. Hence, an attempt has been made to assess their QOL and factors determining them. Method: A convenient sampling technique was used and 114 persons affected with Hansen's disease were studied. The study was conducted for a period of 1 year from November 2012 to October 2013. QOL was assessed using the WHO QOL-BREF Questionnaire and mental health status by the Self-Reporting Questionnaire. The results were obtained using SPSS 17.0 software, statistical tests such as Chi-square test, ANOVA, and standard multiple logistic regression analysis were used. Results: Quality of leprosy patients was poor. The mean WHOQOL-BREF total score was below average (mean score <65). Physical QOL of leprosy was more affected in females (mean WHOQOL-BREF score = 20.80). Mental distress was more prevalent in males (74.6%) compared to females (25.4%). Presence of deformities, female sex of the patient, and advanced age of the patient showed the greatest association with adverse QOL. Conclusion: Presence of physical disabilities or deformities and advanced age of leprosy patients adversely affect QOL of leprosy patients, whereas low level of education and poor socioeconomic status do not have a significant effect on QOL.