Wrist Extensor Tenosynovitis After COVID-19 Vaccination.

We present the case of a 54-year-old right-handed woman with no medical history of rheumatic disease or trauma to the upper extremities who developed painful nodules along her left upper extremity and torso immediately after receiving the mRNA-1273 SARS-CoV-2 vaccine booster for COVID-19 in her left upper extremity. Most of the nodules subsided within several days, but several persisted over the dorsum of the left wrist with physical examination and imaging findings consistent with second and fourth extensor compartment tenosynovitis. She ultimately underwent excision of the left wrist extensor tenosynovitis, followed by a repeat excision for recurrence of symptoms.

Nesfatin-1 is an inhibitor of the growth hormone-insulin-like growth factor axis in goldfish (Carassius auratus).

Nesfatin-1, an 82 amino acid peptide cleaved from the N-terminal of its precursor nucleobindin-2 (NUCB2), is emerging as a multifunctional peptide in fish. The present study aimed to determine whether nesfatin-1 plays a role in fish somatic growth by modulating the growth hormone (GH)/insulin-like growth factor (IGF) axis, using a representative teleost model, the goldfish (Carassius auratus). The results demonstrated that a single i.p. injection of synthetic goldfish nesfatin-1 significantly decreased the expression of hypothalamic pacap (approximately 90%) and pituitary Gh (approximately 90%) mRNAs at 15 minutes post-injection. Serum GH levels were also reduced as a result of nesfatin-1 administration, by approximately 45% and 55% at 15 and 30 minutes post-injection, respectively. Likewise, in vitro treatment of goldfish dispersed pituitary cells with nesfatin-1 reduced Gh secretion, suggesting that nesfatin-1 acts directly on pituitary somatotrophs to inhibit Gh release. Exposure of cultured liver fragments to nesfatin-1 (0.1, 1 and 10 nmol L-1 ) led to a significant reduction in igf-1 mRNA at 120 minutes and of igf-II mRNA at 30 and 60 minutes post-incubation. Collectively, these results indicate a suppressive role for nesfatin-1 on the goldfish GH/IGF axis. Immunohistochemical studies demonstrated that NUCB2/nesfatin-1-like immunoreactivity, although present in the goldfish pituitary, is not colocalised with GH in goldfish somatotrophs. Thus, nesfatin-1 does not appear to act in an autocrine manner to regulate GH secretion. Taken together, this research found that the pituitary gland is an important source of endogenous NUCB2/nesfatin-1 and also that nesfatin-1 directly suppresses the Gh/IGF axis in goldfish.

Frontiers in Multiscale Modeling of Photoreceptor Proteins.

This perspective article highlights the challenges in the theoretical description of photoreceptor proteins using multiscale modeling, as discussed at the CECAM workshop in Tel Aviv, Israel. The participants have identified grand challenges and discussed the development of new tools to address them. Recent progress in understanding representative proteins such as green fluorescent protein, photoactive yellow protein, phytochrome, and rhodopsin is presented, along with methodological developments.

Sarcoma European and Latin American Network (SELNET) Recommendations on Prioritization in Sarcoma Care During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 outbreak has resulted in collision between patients infected with SARS-CoV-2 and those with cancer on different fronts. Patients with cancer have been impacted by deferral, modification, and even cessation of therapy. Adaptive measures to minimize hospital exposure, following the precautionary principle, have been proposed for cancer care during COVID-19 era. We present here a consensus on prioritizing recommendations across the continuum of sarcoma patient care. MATERIAL AND METHODS: A total of 125 recommendations were proposed in soft-tissue, bone, and visceral sarcoma care. Recommendations were assigned as higher or lower priority if they cannot or can be postponed at least 2-3 months, respectively. The consensus level for each recommendation was classified as "strongly recommended" (SR) if more than 90% of experts agreed, "recommended" (R) if 75%-90% of experts agreed and "no consensus" (NC) if fewer than 75% agreed. Sarcoma experts from 11 countries within the Sarcoma European-Latin American Network (SELNET) consortium participated, including countries in the Americas and Europe. The European Society for Medical Oncology-Magnitude of clinical benefit scale was applied to systemic-treatment recommendations to support prioritization. RESULTS: There were 80 SRs, 35 Rs, and 10 NCs among the 125 recommendations issued and completed by 31 multidisciplinary sarcoma experts. The consensus was higher among the 75 higher-priority recommendations (85%, 12%, and 3% for SR, R, and NC, respectively) than in the 50 lower-priority recommendations (32%, 52%, and 16% for SR, R, and NC, respectively). CONCLUSION: The consensus on 115 of 125 recommendations indicates a high-level of convergence among experts. The SELNET consensus provides a tool for sarcoma multidisciplinary treatment committees during the COVID-19 outbreak. IMPLICATIONS FOR PRACTICE: The Sarcoma European-Latin American Network (SELNET) consensus on sarcoma prioritization care during the COVID-19 era issued 125 pragmatical recommendations distributed as higher or lower priority to protect critical decisions on sarcoma care during the COVID-19 pandemic. A multidisciplinary team from 11 countries reached consensus on 115 recommendations. The consensus was lower among lower-priority recommendations, which shows reticence to postpone actions even in indolent tumors. The European Society for Medical Oncology-Magnitude of Clinical Benefit scale was applied as support for prioritizing systemic treatment. Consensus on 115 of 125 recommendations indicates a high level of convergence among experts. The SELNET consensus provides a practice tool for guidance in the decisions of sarcoma multidisciplinary treatment committees during the COVID-19 outbreak.

Dynamic Properties of the Photosensory Domain of Deinococcus radiodurans Bacteriophytochrome.

Phytochromes are biological photoreceptors found in all kingdoms of life. Numerous physicochemical and spectroscopic studies of phytochromes have been carried out for many decades, both experimentally and computationally, with the main focus on the photoconversion mechanism involving a tetrapyrrole chromophore. In this computational work, we concentrate on the long-scale dynamic motion of the photosensory domain of Deinococcus radiodurans by means of classical all-atom molecular dynamics (MD) simulations. Conventional and accelerated MD methods in combination with two different force fields, CHARMM27 and AMBER ff14SB, are tested in long atomistic simulations to confront the dynamics of monomer and dimer forms. These calculations highlight dissimilar equilibrium conformations in aqueous solutions and, in turn, different large-scale dynamic behaviors of the monomer form vs the dimer form. While the phytochrome in a monomer form tends to close the cavity entailed between the GAF and PHY domains, the opposite trend is predicted for the phytochrome dimer, which opens up as a consequence of the formation of strong salt bridges between the PHY domains of two molecules in water.

Preoperative PROMIS Scores Predict Postoperative PROMIS Score Improvement for Patients Undergoing Hand Surgery.

Background: Patient-Reported Outcomes Measurement Information System (PROMIS) can be used alongside preoperative patient characteristics to set postsurgery expectations. This study aimed to analyze whether preoperative scores can predict significant postoperative PROMIS score improvement. Methods: Patients undergoing hand and wrist surgery with initial and greater than 6-month follow-up PROMIS scores were assigned to derivation or validation cohorts, separating trauma and nontrauma conditions. Receiver operating characteristic curves were calculated for the derivation cohort to determine whether preoperative PROMIS scores could predict postoperative PROMIS score improvement utilizing minimal clinically important difference principles. Results: In the nontrauma sample, patients with baseline Physical Function (PF) scores below 31.0 and Pain Interference (PI) and Depression scores above 68.2 and 62.2, respectively, improved their postoperative PROMIS scores with 95%, 96%, and 94% specificity. Patients with baseline PF scores above 52.1 and PI and Depression scores below 49.5 and 39.5, respectively, did not substantially improve their postoperative PROMIS scores with 94%, 93%, and 96% sensitivity. In the trauma sample, patients with baseline PF scores below 34.8 and PI and Depression scores above 69.2 and 62.2, respectively, each improved their postoperative PROMIS scores with 95% specificity. Patients with baseline PF scores above 52.1 and PI and Depression scores below 46.6 and 44.0, respectively, did not substantially improve their postoperative scores with 95%, 94%, and 95% sensitivity. Conclusions: Preoperative PROMIS PF, PI, and Depression scores can predict postoperative PROMIS score improvement for a select group of patients, which may help in setting expectations. Future work can help determine the level of true clinical improvement these findings represent.

Fully Quantum Chemical Treatment of Chromophore-Protein Interactions in Phytochromes.

The intriguing ability of phytochromes to photoconvert between red-absorbing (Pr) and far-red-absorbing (Pfr) states depends on key interactions between a bilin chromophore and protein matrix. However, both the identification of the chemical nature and quantification of chromophore-protein interactions have not been yet fully investigated by experiments or extensive computations. Here, we presented a powerful and straightforward approach based on the fragment molecular orbital method to identify the nature and quantify the strength of the noncovalent interactions at a fully quantum mechanical level between the biliverdin (BV) chromophore and protein matrix of the Deinococcus radiodurans phytochrome (DrBphP) in the Pr state. By using pair interaction energy decomposition analysis approach, the pyrrole water, Asp207, and Glu27 were detected as key residues for the stabilization of the pyrrole rings of the BV chromophore through the formation of six H-bonds. Furthermore, the conserved Arg254 and His260 were also identified as essential residues in the conformational stability of both propionic side chains B and C. Moreover, new interactions were identified in the chromophore-binding pocket, two nonclassical H-bonds (CH/O interactions) between Asp207 and Tyr263, and an OH/π interaction between Tyr263 and ring D of the BV chromophore, which might have photochemical relevance.

Role of the Propionic Side Chains for the Photoconversion of Bacterial Phytochromes.

Bacteriophytochromes harboring a biliverdin IXα (BV) chromophore undergo photoinduced reaction cascades to switch between physiologically inactive and active states. Employing vibrational spectroscopic and computational methods, we analyzed the role of propionic substituents of BV in the transformations between parent states Pr and Pfr in prototypical (Agp1) and bathy (Agp2) phytochromes from Agrobacterium fabrum. Both proteins form adducts with BV monoesters (BVM), esterified at propionic side chain B (PsB) or C (PsC), but in each case, only one monoester adduct is reactive. In the reactive Agp2-BVM-B complex (esterified at ring B), the Pfr dark state displays the structural properties characteristic of bathy phytochromes, including a protonated PsC. As in native Agp2, PsC is deprotonated in the final step of the Pfr phototransformation. However, the concomitant α-helix/ß-sheet secondary structure change of the tongue is blocked at the stage of unfolding of the coiled loop region. This finding and the shift of the tautomeric equilibrium of BVM toward the enol form are attributed to the drastic changes in the electrostatic potential. The calculations further suggest that deprotonation of PsC and the protonation state of His278 control the reactivity of the enol tautomer, thereby accounting for the extraordinarily slow thermal reversion. Although strong perturbations of the electrostatic potential are also found for Agp1-BVM, the consequences for the Pr-to-Pfr phototransformation are less severe. Specifically, the structural transition of the tongue is not impaired and thermal reversion is even accelerated. The different response of Agp1 and Agp2 to monoesterification of BV points to different photoconversion mechanisms.

Depression and Pain Interference Correlate With Physical Function in Patients Recovering From Hand Surgery.

Background: Patient-reported outcome measures vary more than expected based on underlying pathology, in part due to the substantial influence of mood and coping strategies. Methods: This study addressed the primary null hypothesis that the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function score 1 month (range, 3-8 weeks) after hand surgery is not associated with PROMIS Depression and PROMIS Pain Interference scores prior to surgery, accounting for other factors. Using an institution-wide database of routinely collected patient-reported outcomes, we identified adult patients who underwent wrist ganglion excision, trapeziometacarpal arthroplasty, hand ganglion excision, trigger digit, De Quervain, and carpal tunnel release. Measures collected included the PROMIS Physical Function Computerized Adaptive Test (CAT), PROMIS Pain Interference CAT, and PROMIS Depression CAT. We sought factors associated with postsurgical PROMIS Physical Function scores and change between preoperative and postoperative score using multivariable linear regression, accounting for age, sex, surgery type, provider, and time from surgery to postsurgical measurement. Results: Higher postoperative PROMIS Physical Function score was independently associated with lower PROMIS Pain Interference scores, lower PROMIS Depression scores, younger age, and treatment by provider team 3. Greater change in PROMIS Physical Function score was independently associated with greater PROMIS Pain Interference scores, greater time from surgery, and treatment by provider team 3. Conclusions: Mood and effective coping strategies affect the level of symptoms and limitations during recovery from hand surgery and represent important treatment opportunities for enhancing recovery.

Novel genes and mutations in patients affected by recurrent pregnancy loss.

Recurrent pregnancy loss is a frequently occurring human infertility-related disease affecting ~1% of women. It has been estimated that the cause remains unexplained in >50% cases which strongly suggests that genetic factors may contribute towards the phenotype. Concerning its molecular aetiology numerous studies have had limited success in identifying the disease's genetic causes. This might have been due to the fact that hundreds of genes are involved in each physiological step necessary for guaranteeing reproductive success in mammals. In such scenario, next generation sequencing provides a potentially interesting tool for research into recurrent pregnancy loss causative mutations. The present study involved whole-exome sequencing and an innovative bioinformatics analysis, for the first time, in 49 unrelated women affected by recurrent pregnancy loss. We identified 27 coding variants (22 genes) potentially related to the phenotype (41% of patients). The affected genes, which were enriched by potentially deleterious sequence variants, belonged to distinct molecular cascades playing key roles in implantation/pregnancy biology. Using a quantum chemical approach method we established that mutations in MMP-10 and FGA proteins led to substantial energetic modifications suggesting an impact on their functions and/or stability. The next generation sequencing and bioinformatics approaches presented here represent an efficient way to find mutations, having potentially moderate/strong functional effects, associated with recurrent pregnancy loss aetiology. We consider that some of these variants (and genes) represent probable future biomarkers for recurrent pregnancy loss.

New mutations in non-syndromic primary ovarian insufficiency patients identified via whole-exome sequencing.

STUDY QUESTION: Is it possible to identify new mutations potentially associated with non-syndromic primary ovarian insufficiency (POI) via whole-exome sequencing (WES)? SUMMARY ANSWER: WES is an efficient tool to study genetic causes of POI as we have identified new mutations, some of which lead to protein destablization potentially contributing to the disease etiology. WHAT IS KNOWN ALREADY: POI is a frequently occurring complex pathology leading to infertility. Mutations in only few candidate genes, mainly identified by Sanger sequencing, have been definitively related to the pathogenesis of the disease. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study performed on 69 women affected by POI. PARTICIPANTS/MATERIALS, SETTING, METHODS: WES and an innovative bioinformatics analysis were used on non-synonymous sequence variants in a subset of 420 selected POI candidate genes. Mutations in BMPR1B and GREM1 were modeled by using fragment molecular orbital analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Fifty-five coding variants in 49 genes potentially related to POI were identified in 33 out of 69 patients (48%). These genes participate in key biological processes in the ovary, such as meiosis, follicular development, granulosa cell differentiation/proliferation and ovulation. The presence of at least two mutations in distinct genes in 42% of the patients argued in favor of a polygenic nature of POI. LIMITATIONS, REASONS FOR CAUTION: It is possible that regulatory regions, not analyzed in the present study, carry further variants related to POI. WIDER IMPLICATIONS OF THE FINDINGS: WES and the in silico analyses presented here represent an efficient approach for mapping variants associated with POI etiology. Sequence variants presented here represents potential future genetic biomarkers. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Universidad del Rosario and Colciencias (Grants CS/CIGGUR-ABN062-2016 and 672-2014). Colciencias supported Liliana Catherine Patiño´s work (Fellowship: 617, 2013). The authors declare no conflict of interest.

Revisiting the Dielectric Constant Effect on the Nucleophile and Leaving Group of Prototypical Backside SN2 Reactions: A Reaction Force and Atomic Contribution Analysis.

The solvent effect on the nucleophile and leaving group atoms of the prototypical F- + CH3Cl → CH3F + Cl- backside bimolecular nucleophilic substitution reaction (SN2) is analyzed employing the reaction force and the atomic contributions methods on the intrinsic reaction coordinate (IRC). Solvent effects were accounted for using the polarizable continuum solvent model. Calculations were performed employing 11 dielectric constants, ε, ranging from 1.0 to 78.5, to cover a wide spectrum of solvents. The reaction force data reveal that the solvent mainly influences the region of the IRC preceding the energy barrier, where the structural rearrangement to reach the transition state occurs. A detailed analysis of the atomic role in the reaction as a function of ε reveals that the nucleophile and the carbon atom are the ones that contribute the most to the energy barrier. In addition, we investigated the effect of the choice of nucleophile and leaving group on the ΔE0 and ΔE‡ of Y- + CH3X → YCH3 + X- (X, Y = F, Cl, Br, I) in aqueous solution. Our analysis allowed us to find relationships between the atomic contributions to the activation energy and leaving group ability and nucleophilicity.

Long-term infusion of nesfatin-1 causes a sustained regulation of whole-body energy homeostasis of male Fischer 344 rats.

Nesfatin-1, the N-terminal fragment of nucleobindin 2 (NUCB2), is an 82 amino-acid peptide that inhibits food intake and exerts weight-reducing effects. Nesfatin-1 has been proposed as a potential anti-obesity peptide. However, studies to date have mainly focused on the acute satiety effects of centrally administered nesfatin-1. The main objective of our studies was to characterize the long-term/chronic effects of peripheral administration of nesfatin-1 on whole-body energy balance and metabolic partitioning in male Fischer 344 rats. Short-term (1 day) subcutaneous infusion of nesfatin-1 (50 µg/kg body weight/day) using osmotic mini-pumps increased spontaneous physical activity and whole-body fat oxidation during the dark phase. This was accompanied by decreased food intake and basal metabolic rate compared to saline infused controls. On the seventh day of nesfatin-1 infusion, cumulative food intake, and total spontaneous physical activity during the dark phase were significantly reduced and elevated, respectively. Meanwhile, intraperitoneal injection of nesfatin-1 only caused a dark phase specific reduction in food intake and an increase in physical activity. NUCB2 mRNA expression in the brain and stomach, as well as serum NUCB2 concentrations were significantly reduced after 24 h fasting, while a post-prandial increase in serum NUCB2 was found in ad libitum fed rats. Collectively, our results indicate that chronic peripheral administration of nesfatin-1 at the dose tested, results in a sustained reduction in food intake and modulation of whole body energy homeostasis.

Practical implications of pre-employment nurse assessments.

Hiring nurses is a difficult task that can have serious repercussions for medical facilities. If nurses without proper skills are hired, patients can suffer from insufficient quality of care and potentially life-threatening conditions. Nurse applicants' technical knowledge is extremely important to avoid negative outcomes; however, there are soft skills that factor into their success, such as bedside manner, personality, communication, and decision making. In order for medical facilities to select and maintain high-performing nurse staff, hiring managers must incorporate evaluations for these types of skills in their hiring process. The current study focused on using content/criterion-related validation design to create assessments by which nurse applicants can be evaluated for both technical knowledge/skills and soft skills. The study included participation of more than 876 nursing staff members. To rank applicants on divergent skills, 3 assessment types were investigated, resulting in the creation of an assessment with 3 components. The clinical, situational, and behavioral components that were created measure applicants' job knowledge, interpersonal competency in medical facility-related situations, and aspects of personality and behavior, respectively. Results indicate that using the assessment can predict 45% of a nurse applicant's future job performance. Practical implications include hiring and maintaining a higher quality of nurses and decreased hiring costs.

Orthophosphate Leaching in St. Augustinegrass and Zoysiagrass Grown in Sandy Soil under Field Conditions.

Phosphorus (P) is required to maintain healthy, high-quality, warm-season turf. However, excessive P applications to soils with poor P retention capabilities may lead to leaching losses to groundwater. This field study was conducted to determine the maximum P fertilizer application rate to (Walt.) [Kuntze] 'Floratam' St. Augustinegrass (St. Augustinegrass) and 'Empire' zoysiagrass (zoysiagrass) below which P leaching is minimized. Five P levels ranging from 0 to 5.0 g P m yr were surface applied as triple superphosphate. Turf was established on an uncoated, low-P sand with negligible P retention capacity. Leaf and root growth, tissue P concentration, soil P concentration, soil P saturation, leachate volume, and orthophosphate (P) concentration in leachates were measured. Mehlich 1-extractable soil P (M1-P) and soil P saturation ratio (PSR) increased with time as the P rate increased. Lower M1-P and PSR values were measured with St. Augustinegrass, which absorbed more P than did zoysiagrass. The root system of St. Augustinegrass was larger and deeper compared with zoysiagrass, promoting greater P uptake and less P leaching. If tissue analysis indicates that P fertilization is required and the soil has the capacity to retain additional P, application of 0.8 g P m yr to zoysiagrass and 1.07 g P m yr to St. Augustinegrass is appropriate and does not result in increased P leaching.

Nesfatin-1 regulates the hypothalamo-pituitary-ovarian axis of fish.

Nesfatin-1 is an anorexigen in goldfish. In the present study, we provide novel data indicating the presence and regulatory effects of nesfatin-1 on the hypothalamo-pituitary-ovarian (HPO) axis of goldfish. Nucleobindin-2 (NUCB2)/nesfatin-1-like immunoreactive (ir) cells are present in the hypothalamus and in the pituitary, suggesting a hypophysiotropic role for nesfatin-1. NUCB2/nesfatin-1-like ir cells colocalize gonadotropin-releasing hormone (GnRH) in the nucleus lateralis tuberis posterioris and the nucleus anterior tuberis of the goldfish hypothalamus. The presence of nesfatin-1 with GnRH in these two nuclei implicated in pituitary hormone release suggests a role for nesfatin-1 on gonadotropin secretion. A single i.p. injection of synthetic goldfish nesfatin-1 (50 ng/g body wt) resulted in an acute decrease (∼75%) in the expression of hypothalamic chicken GnRH-II and salmon GnRH mRNAs at 15 min postinjection in goldfish. Meanwhile, pituitary luteinizing hormone (LH) beta and follicle-stimulating hormone beta mRNAs were also inhibited (∼80%), but only at 60 min postinjection. Nesfatin-1 administration also resulted in a significant reduction (∼60%) in serum LH levels at 60 min postadministration. Nesfatin-1-like immunoreactivity was also found in the follicle cells, but not the oocytes, in zebrafish and goldfish ovaries. Incubation of zebrafish follicles with nesfatin-1 resulted in a significant reduction in basal germinal vesicle breakdown (∼50%) during the oocyte maturation. In addition, nesfatin-1 also attenuated the stimulatory effects of maturation-inducing hormone on germinal vesicle breakdown. Together, the current results indicate that nesfatin-1 is a metabolic hormone with an inhibitory tone on fish reproduction. Nesfatin-1 appears to elicit this suppressive effect through actions on all three tissues in the fish HPO axis.

1-(2,4-Difluoro-phen-yl)-2-(1H-1,2,4-triazol-1-yl)ethanol.

In the title compound, C(10)H(9)F(2)N(3)O, the dihedral angle between the mean planes of the triazole and benzene rings is 20.6 (2)°. In the crystal, mol-ecules are linked by strong O-H⋯ N hydrogen bonds into chains with graph-set notation C(9) along [100]. Weak C-H⋯N and C-H⋯F inter-actions are also observed.

Nucleobindins: bioactive precursor proteins encoding putative endocrine factors?

The nucleobindins, nucleobindin 1 (NUCB1) and nucleobindin 2 (NUCB2), are homologous multidomain calcium and DNA binding proteins. NUCB1 is a well-characterized Golgi protein found within the rat pituitary, liver and kidney with functions related to immunity, calcium homeostasis and G protein signaling. NUCB2 is found both in the hypothalamus and brain stem centers, as well as peripherally in the digestive tract. Renewed interest in the nucleobindins has been sparked by the recent discovery of nesfatin-1, an endocrine factor post-translationally processed from the N-terminal of NUCB2. Nesfatin-1 has quickly established itself as a novel regulator of appetite, insulin secretion, energy homeostasis and reproduction with important consequences to the etiology of metabolic diseases including diabetes and obesity. The discovery of nesfatin-1 and it endocrine functions attracted more attention to the nucleobindins that are already known to have important intracellular functions. From the sequence information available, it is possible that nucelobindins itself or nesfatin-1 like peptides within the NUCB1 could also elicit nesfatin-1-like biological functions. The research on nesfatin-1 in last 5years further adds to the importance of nucleobindins as potential endocrine precursors. This review aims to summarize some of the most recent findings on the functional significance of NUCB1, NUCB2, as well as encoded proteins and highlights the questions that remain unanswered.