A ZPR1 mutation is associated with a novel syndrome of growth restriction, distinct craniofacial features, alopecia, and hypoplastic kidneys.

A novel autosomal recessive disorder characterized by pre- and postnatal growth restriction with microcephaly, distinctive craniofacial features, congenital alopecia, hypoplastic kidneys with renal insufficiency, global developmental delay, severe congenital sensorineural hearing loss, early mortality, hydrocephalus, and genital hypoplasia was observed in 4 children from 3 families of New Mexican Hispanic heritage. Three of the children died before 3 years of age from uremia and/or sepsis. Exome sequencing of the surviving individual identified a homozygous c.587T>C (p.Ile196Thr) mutation in ZPR1 Zinc Finger (ZPR1) that segregated appropriately in her family. In a second family, the identical variant was shown to be heterozygous in the affected individual's parents and not homozygous in any of her unaffected siblings. ZPR1 is a ubiquitously expressed, highly conserved protein postulated to transmit proliferative signals from the cell membrane to the nucleus. Structural modeling reveals that p.Ile196Thr disrupts the hydrophobic core of ZPR1. Patient fibroblast cells showed no detectable levels of ZPR1 and the cells showed a defect in cell cycle progression where a significant number of cells remained arrested in the G1 phase. We provide genetic and molecular evidence that a homozygous missense mutation in ZPR1 is associated with a rare and recognizable multisystem syndrome.

The last link of the x-aminobutyric acid series: the five conformers of ß-aminobutyric acid.

ß-Aminobutyric acid is a non-proteinogenic amino acid that is known to protect plants against various pathogens. Its structure is midway between α-aminobutyric acid and γ-aminobutyric acid. The structural differences in the position of the amino group in the conformational stabilization of ß-aminobutyric acid have been studied by laser ablation Fourier transform microwave spectroscopy. Five conformers have been detected, and their rotational and quadrupole coupling constants of the 14N nucleus determined. Three of the conformers, including the most stable structure, are stabilized by a non-bifurcated N-HO[double bond, length as m-dash]C intramolecular hydrogen bond. The other two conformers possess a NH-O intramolecular interaction. In this work we highlight that ß-aminobutyric acid shows the conformational peculiarities of α-aminobutyric acid and γ-aminobutyric acid completing the rotational spectroscopic study of the x-aminobutyric acid series.

Stem cells and G-CSF for treating neuroinflammation in traumatic brain injury: aging as a comorbidity factor.

Traumatic brain injury (TBI), often called the signature wound of Iraq and Afghanistan wars, is characterized by a progressive histopathology and long-lasting behavioral deficits. Treatment options for TBI are limited and patients are usually relegated to rehabilitation therapy and a handful of experimental treatments. Stem cell-based therapies offer alternative treatment regimens for TBI, and have been intended to target the delayed therapeutic window post-TBI, in order to promote "neuroregeneration," in lieu of "neuroprotection" which can be accomplished during acute TBI phase. However, these interventions may require adjunctive pharmacological treatments especially when aging is considered as a comorbidity factor for post-TBI health outcomes. Here, we put forward the concept that a combination therapy of human umbilical cord blood cell (hUCB) and granulocyte-colony stimulating factor (G-CSF) attenuates neuroinflammation in TBI, in view of the safety and efficacy profiles of hUCB and G-CSF, their respective mechanisms of action, and efficacy of hUCB+G-CSF combination therapy in TBI animal models. Further investigations on the neuroinflammatory pathway as a key pathological hallmark in acute and chronic TBI and also as a major therapeutic target of hUCB+G-CSF are warranted in order to optimize the translation of this combination therapy in the clinic.

Conformers of ß-aminoisobutyric acid probed by jet-cooled microwave and matrix isolation infrared spectroscopic techniques.

ß-aminoisobutyric acid (BAIBA) has been studied in isolation conditions: in the gas phase and trapped into a cryogenic N2 matrix. A solid sample of the compound was vaporized by laser ablation and investigated through their rotational spectra in a supersonic expansion using two different spectroscopic techniques: broadband chirped pulse Fourier transform microwave spectroscopy and conventional molecular beam Fourier transform microwave spectroscopy. Four conformers with structures of two types could be successfully identified by comparison of the experimental rotational and (14)N nuclear quadruple coupling constants with those predicted theoretically: type A, bearing an OH⋯N intramolecular hydrogen bond and its carboxylic group in the trans geometry (H-O-C=O dihedral ∼180°), and type B, having an NH⋯O bond and the cis arrangement of the carboxylic group. These two types of conformers could also be trapped from the gas phase into a cryogenic N2 matrix and probed by Fourier transform infrared (IR) spectroscopy. In situ irradiation of BAIBA isolated in N2 matrix of type B conformers using near-IR radiation tuned at the frequency of the O-H stretching 1st overtone (∼6930 cm(-1)) of these forms allowed to selectively convert them into type A conformers and into a new type of conformers of higher energy (type D) bearing an NH⋯O=C bond and a O-H "free" trans carboxylic group.

In vivo behavior of complete human oral mucosa equivalents: characterization in athymic mice.

BACKGROUND AND OBJECTIVE: The interest in tissue engineering as a way to achieve repair of damaged body tissues has led to the carrying out of many studies whose results point to the potential effectiveness of these methods. In a previous study, we reported the obtaining of complete autologous oral mucosa equivalents (CAOMEs), characterized by oral immature keratinocytes and stem cells on an autologous plasma and fibroblast scaffold. The purpose of this study is to show their behavior in vivo, by using them as free grafts in experimental animals, and to demonstrate their potential capacity to regenerate oral mucosa. MATERIAL AND METHODS: We engineered CAOMEs, as previously described. All CAOMEs thus obtained were used as free grafts in nu/nu mice. To assess their evolution in vivo, we studied their histological and immunohistochemical features by using AE1/AE3 pancytokeratin, the 5/6 cytokeratin pair, cytokeratin 13, laminin 5, collagen IV, vimentin, p-63 and Ki-67, at 7, 14 and 21 d. RESULTS: The structure became progressively closer to that of oral mucosa samples. Cytokeratin 5/6 staining became increasingly intense in the basal and suprabasal layers, and cytokeratin 13 was exclusively positive in the superficial layers. The basal membrane was completed in 21 d. Vimentin showed a correct formation of the chorion. The increasingly positive staining of p-63 and Ki-67 indicated that the regeneration process was taking place. CONCLUSION: The present study shows the potential regenerative capacity of the CAOMEs by their ability to reach maturity similar to that seen in oral mucosa.

Rapid probe of the nicotine spectra by high-resolution rotational spectroscopy.

Nicotine has been investigated in the gas phase and two conformational forms were characterized through their rotational spectra. Two spectroscopic techniques have been used to obtain the spectra: a new design of broadband Fourier transform microwave (FTMW) spectroscopy with an in-phase/quadrature-phase-modulation passage-acquired-coherence technique (IMPACT) and narrowband FTMW spectroscopy with coaxially oriented beam-resonator arrangement (COBRA). The rotational, centrifugal distortion and hyperfine quadrupole coupling constants of two conformers of nicotine have been determined and found to be in N-methyl trans configurations with the pyridine and pyrrolidine rings perpendicular to one another. The quadrupole hyperfine structure originated by two (14)N nuclei has been completely resolved for both conformers and used for their unambiguous identification.

Engineering care transitions: Clinician perceptions of barriers to safe medication management during transitions of patient care.

Medication safety during care transitions is a significant challenge, especially for older adults prescribed multiple medications. Using a systems approach to understand barriers to and strategies for safe medication management throughout high-risk periods of hospital-to-home transition is one important step in designing effective interventions. Framing the care transition as a collaboration between healthcare and patient "work systems," we conducted semi-structured interviews with 37 clinical team members, representing 10 different professional roles involved in providing transitional care for patients. Thematic analyses identified key strategies used by clinical team members in preparing patients to self-manage medications safely in the home environment: (1) streamlining and coordinating clinical management of medication reconciliation across care settings; (2) building patient capacity and engagement in self-management of medications; and (3) redesigning the transitional process. Our research highlights the value in aligning professionals' care transition goals with patients and caregiver(s) to better prepare them to self-manage medications upon discharge.

Studies on Raspy Crickets: A new Andean Hyperbaenini genus (Orthoptera: Gryllacrididae: Hyperbaeninae).

Mikrohyperbaenus n. gen. is the first Andean genus for the tribe Hyperbaenini, the other genera such as Hyperbaenus and Dibelona inhabit the low and humid lands of South America. The new genus is distinguished by the structure of the male terminalia and the apex of the labial and maxillary palps, which are unusually naked or without the cuticle, that covers the other body segments. Mikrohyperbaenus n. gen. is a monotypic genus, found in the surroundings of the Zapatoca municipality, Santander, Colombia, a territory inhabited in the past by the Guane indigenous people, for which the new species Mikrohyperbaenus guane n. gen. et n. sp. is dedicated to that particular Pre-columbian indigenous people.

In vitro engineering of complete autologous oral mucosa equivalents: characterization of a novel scaffold.

BACKGROUND AND OBJECTIVE: Restoration of oral mucosa defects by means of in vitro-cultured equivalents has become a valid alternative in the field of oral and periodontics surgery. Although different techniques have been described, none has been able to provide an equivalent with an autologous scaffold for the epithelium. The purpose of this study was to obtain complete autologous oral mucosa equivalents (CAOME) using the patient's own fibroblasts and plasma and to characterize these equivalents both morphologically and immunohistochemically. MATERIAL AND METHODS: We acquired cell types (keratinocytes and fibroblasts) from the same mucosal samples, which were taken from healthy patients who underwent oral surgery. To construct the CAOME, a small sample of blood was obtained from the patient and subsequently processed to obtain a fibrin glue scaffold. All CAOME thus obtained were stained using the standard hematoxylin and eosin method to study their morphological characteristics. To establish the type of cells in the epithelial layer, CAOME were stained with pancytokeratin AE1/AE3, cytokeratins 5/6 and 13, p-63 and Ki-67. Finally, laminin 5 and collagen IV were used to reveal the presence of a basal membrane. RESULTS: The CAOME featured a monolayer of cube-shaped epithelial cells similar to that found on the basal layer of the oral mucosa. Close to the epithelial layer lay the fibrin and fibroblasts-embedded scaffold. The CAOME was positive to pancytokeratin AE1/AE3, cytokeratin 5/6 and p-63. No reaction was found to cytokeratin 13 and Ki-67. There was staining to laminin 5 but not to collagen IV. CONCLUSIONS: It is possible to engineer a CAOME with an epithelium of basal-like and immature keratinocytes, which could potentially reconstruct in vivo loss of tissue.

Parry-Romberg Syndrome and Temporal Lobe Refractory Epilepsy: Case Report.

The Parry-Romberg syndrome (PRS), also known as hemifacial atrophy, is a rare neurocutaneous disease with the prevalence of 1/700,000 cases. It is more common in women than men, with an early onset of disease usually within the first two decades of life. Even though the etiology of PRS is unknown, it is thought to be a multifactorial disease that involves hereditary, posttraumatic, autoimmune, infectious, and neoplastic factors. There are a variety of systemic manifestations described in PRS including neurological conditions that range from intractable headache to refractory epilepsy. The manifestations must be identified in a timely manner to ensure an early therapeutic intervention, considering that an appropriate approach during the initial phase might halt the disease progression and markedly improve the quality of life in these patients. This article is aimed to describe the case of a 23 years old female with left hemifacial atrophy and dermatologic, dental, and neurologic compromise, associated with refractory temporal lobe epilepsy evidenced in neuroimaging and electrodiagnostic testings.

Effective Tityus serrulatus anti-venom produced using the Ts1 component.

Scorpion stings are a public health problem in Brazil, with most incidents involving the species Tityus serrulatus. Some T. serrulatus toxins may act as immunogens for the production of a specific anti-venom, but many of the component toxins remain poorly characterized. Here, we describe the immunological characteristics of the toxin Ts1 (also known as TsVII and Ts-gamma) and evaluate production of neutralizing antibodies against the crude venom of T. serrulatus. Recombinant Ts1 with one copy (Ts1(1)) or two copies in tandem (Ts1(2)) was expressed in BL21 (DE3) cells. Rabbits and mice were immunized with the recombinant proteins (inclusion bodies) and then tested for production of neutralizing antibodies. Neutralization assays showed that anti-Ts1(1) and anti-Ts1(2) protected animals challenged with T. serrulatus crude venom and native Ts1. Thus, Ts1 could be used in a mixed "cocktail" of immunogens for T. serrulatus anti-venom production.

A procedure to recruit members to enlarge protein family databases--the building of UECOG (UniRef-Enriched COG Database) as a model.

A procedure to recruit members to enlarge protein family databases is described here. The procedure makes use of UniRef50 clusters produced by UniProt. Current family entries are used to recruit additional members based on the UniRef50 clusters to which they belong. Only those additional UniRef50 members that are not fragments and whose length is within a restricted range relative to the original entry are recruited. The enriched dataset is then limited to contain only genomes from selected clades. We used the COG database - used for genome annotation and for studies of phylogenetics and gene evolution - as a model. To validate the method, a UniRef-Enriched COG0151 (UECOG) was tested with distinct procedures to compare recruited members with the recruiters: PSI-BLAST, secondary structure overlap (SOV), Seed Linkage, COGnitor, shared domain content, and neighbor-joining single-linkage, and observed that the former four agree in their validations. Presently, the UniRef50-based recruitment procedure enriches the COG database for Archaea, Bacteria and its subgroups Actinobacteria, Firmicutes, Proteobacteria, and other bacteria by 2.2-, 8.0-, 7.0-, 8.8-, 8.7-, and 4.2-fold, respectively, in terms of sequences, and also considerably increased the number of species.

Laboratory rotational spectrum and astronomical search for methoxyacetaldehyde.

CONTEXT: Methoxyacetaldehyde belongs to a group of structural isomers with the general formula C3H6O2, of which methyl acetate and ethyl formate are known interstellar molecules. Rotational data available for methoxyacetaldehyde are limited to 40 GHz, which makes predictions at higher frequencies rather uncertain. AIMS: The aim of this work is to provide accurate experimental frequencies of methoxyacetaldehyde in the millimeter-wave region to support its detection in the interstellar medium. METHODS: The rotational spectrum of methoxyacetaldehyde was recorded at room-temperature from 75 to 120 GHz and from 170 to 310 GHz using the millimeter-wave spectrometer in Valladolid. Additional measurements were also performed at conditions of supersonic expansion from 6 to 18 GHz. The assigned rotational transitions were analyzed using the S -reduced semirigid-rotor Hamiltonian. RESULTS: We newly assigned over 1000 lines for the most stable conformer of methoxyacetaldehyde in its ground state and five lowest excited vibrational states, and precise sets of spectroscopic constants were obtained. We searched for spectral features of methoxyacetaldehyde in the high-mass star-forming regions Orion KL and Sagittarius B2, as well as in the cold dark cloud Barnard 1 (B1-b). No lines belonging to methoxyacetaldehyde were detected above the detection limit of our data. We provide upper limits to the methoxyacetaldehyde colum density in these sources.

Transcriptional profiling of SHR/NCrl prefrontal cortex shows hyperactivity-associated genes responsive to amphetamine challenge.

Several studies suggest a strong genetic component of attention-deficit/hyperactivity disorder (ADHD), a complex neurodevelopmental disorder characterized by inappropriate levels of hyperactivity, impulsivity and inattention. Determining specific genetic risk variants for each symptom dimension of ADHD may aid in the identification of the biological risk factors of the disorder. In this study, we explored the potential genetic underpinnings of the hyperactive phenotype of ADHD. To this end, we examined differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of SHR/NCrl, an animal model of ADHD, compared with its genetic control, the Wistar Kyoto (WKY/NCrl) rat and the Wistar rat, strain used to represent the 'normal' heterogeneous population. Relative to WKY/NCrl and Wistar controls, SHR/NCrl showed hyperactivity in the open-field test. Treatment with the ADHD drug, amphetamine (AMPH) reduced hyperactivity in SHR/NCrl. Meanwhile, AMPH increased locomotor activity in WKY/NCrl and Wistar rats. Gene expression analysis found 21 common upregulated and 36 downregulated genes in the PFC of drug-naive SHR/NCrl when compared with WKY/NCrl and Wistar rats. Of these DEGs, expression levels of two genes, Atxn7 and Per2, which are involved in transcription and circadian rhythm, respectively, were downregulated following AMPH treatment in SHR/NCrl. Quantitative real-time-polymerase chain reaction analyses verified expression patterns of these genes in the PFC of drug-naïve and AMPH-treated SHR/NCrl. The present findings indicate genetic risk variants that may be associated with the hyperactive phenotype in ADHD. Further studies are warranted to establish the roles of Atxn7 and Per2 in mediating hyperactivity.

Useful independent factors for distinguish infection and colonization in patients with urinary carbapenemase-producing Enterobacteriaceae isolation.

OBJECTIVE: The aim of this study is to know epidemiologic and clinical differences among those patients colonized or infected by carbapenemase-producing Enterobacteriaceae (CPE) and develop a predictive model to facilitate the clinical approach concerning to start antimicrobial therapy. METHODS: Observational retrospective cohort study was performed involving all patients with Urine carbapenemase-producing Enterobacteriaceae isolation (UCPEI) between November 2013 and July 2015. Patients were classifieds as colonized or infected considering Center for Disease Control and Prevention (CDC) definition for urinary tract infection (UTI). RESULTS: A total of 72 patients were included, mean age 76.4 (IQR 23-99) years and 40 (55.6%) were women. Thirty-four (47.2%) were colonized and 38 (52.8%) met the criteria of UTI and were considered infected. The independent variables associated to infection were female sex, peripheral vascular disease, admission in medical ward, permanent urinary catheter carrier, previous antimicrobial therapy, and length of stay. Isolation of OXA-48 carbapenemase-producing Enterobacteriaceae behaved as a non UTI (colonization) factor in comparison with KPC or VIM CPE. The developed predictive model showed an area under the curve (AUC) of 0.901 (95% CI: 0.832-0.970; p < 0.001). CONCLUSIONS: The predictive model that includes all this factors has demonstrated a good accuracy for infection diagnosis in these patients, an important issue considering that establishing the diagnosis of infection is not always easy in the profile of patients in which a CPE is isolated.

The use of piezoelectric surgery to lateralize the inferior alveolar nerve with simultaneous implant placement and immediate buccal cortical bone repositioning: a prospective clinical study.

A prospective study was conducted to assess a variation of inferior alveolar nerve (IAN) lateralization. This study included 13 patients. An osteotomy was made with a piezoelectric device, and the IAN bundle was moved buccally. Dental implants were then inserted medial to the nerve bundle, and the inner surface of the buccal cortical bone plate was shaped to reduce its thickness. Finally, the bone plate was repositioned to restore the original shape and contour of the mandible. Neurosensory examinations of the lower lip and chin were performed using three tests: light touch, pain, and two-point discrimination. Three months after surgery, the function of the IAN was judged to be completely restored at 11 of the 13 surgical sites. Differences in the tests comparing the operated and non-operated sides were not significant. No implants were lost, and all patients were satisfied with the result. Although IAN lateralization in conjunction with dental implant placement is rarely indicated, the use of a piezoelectric device to perform a buccal osteotomy with final repositioning of the buccal cortical plate over the bony defect contributes to the recovery of the contour and shape of the mandible, without impairment of IAN function.

High-Resolution Rotational Spectrum, Dunham Coefficients, and Potential Energy Function of NaCl.

We report laboratory spectroscopy for the first time of the J = 1-0 and J = 2-1 lines of Na35Cl and Na37Cl in several vibrational states. The hyperfine structure has been resolved in both transitions for all vibrational levels, which permit us to predict with high accuracy the hyperfine splitting of the rotational transitions of the two isotopologues at higher frequencies. The new data have been merged with all previous works at microwave, millimeter, and infrared wavelengths and fitted to a series of mass-independent Dunham parameters and to a potential energy function. The obtained parameters have been used to compute a new dipole moment function, from which the dipole moment for infrared transitions up to Δv = 8 has been derived. Frequency and intensity predictions are provided for all rovibrational transitions up to J = 150 and v = 8, from which the ALMA data of evolved stars can be modeled and interpreted.

Hints of a rotating spiral structure in the innermost regions around IRC +10216.

The Atacama Large Millimeter/submillimeter Array (ALMA) is allowing us to study the innermost regions of the circumstellar envelopes of evolved stars with un-precedented precision and sensitivity. Key processes in the ejection of matter and dust from these objects occur in their inner zones. In this work, we present sub-arcsecond interferometric maps of transitions of metal-bearing molecules towards the prototypical C-rich evolved star IRC +10216. While Al-bearing molecules seem to be present as a roughly spherical shell, the molecular emission from the salts NaCl and KCl presents an elongation in the inner regions, with a central minimum. In order to accurately analyze the emission from the NaCl rotational lines, we present new calculations of the collisional rates for this molecule based on new spectroscopic constants. The most plausible interpretation for the spatial distribution of the salts is a spiral with a NaCl mass of 0.08M☉. Alternatively, a torus of gas and dust would result in similar structures as those observed. From the torus scenario we derive a mass of ~ 1.1 × 10-4M☉. In both cases, the spiral and the torus, the NaCl structure presents an inner minimum of 27 AU. In the case of the torus, the outer radius is 73 AU. The kinematics of both the spiral and the torus suggests that they are slowly expanding and rotating. Alternative explanations for the presence of the elongation are explored. The presence of these features only in KCl and NaCl might be a result of their comparatively high dipole moment with respect to the Al-bearing species.

Preparation and Characterization of Coaxial Electrospun Fibers Containing Triclosan for Comparative Study of Release Properties with Amoxicillin and Epicatechin.

The optimal conditions for the fibers preparation of cellulose acetate (CA) and poly(vinyl pyrrolidone) (PVP) containing triclosan within the fiber were successfully found; the physicochemical characteristics of these fibrous membranes were corroborated by FTIR spectroscopy, thermal analysis, mechanical tests, SEM , and TEM analysis. The formation of composite fibers of CA and PVP containing triclosan at the core of the fiber was evidenced. A comparative study of the release properties of amoxicillin, epicatechin or triclosan embedded into fibers CA/PVP/CA was performed. As more interactions of the drug with CA or PVP occur, slower release of the drug into the release medium takes place. Regarding the drug delivery system design, it is important to consider the possible molecular interactions between the material components and predict how fast or slow the drug will be delivered into the corresponding medium.

The relationship between climate and the distribution of Culicoides imicola in Iberia.

The biting midge Culicoides imicola was captured at 17 of 27 farms in Spain and Portugal during a survey of its distribution following outbreaks of African horse sickness in Iberia that occurred between 1987 and 1990. Farms were sampled approximately twice weekly from October 1992 to February 1995. Farms were widely spaced apart (maximum 850 km) and had considerable variation in climate. Across sites, summer temperatures ranged from 18.3 degrees C-27.2 degrees C; in winter the range was 4.4 degrees C-11.6 degrees C. Relative humidities in summer ranged from 37.2% to 90.1%. Proximity to southern Spain (Seville) was the most significant predictor of the presence/absence of C. imicola, but high summer temperatures and possibly dry summer conditions, were also important. Vila Nova de Milfontes in Portugal, where C. imicola was abundant and the climate is relatively cool, was an exception to the climatic trends at the other 26 sites. This exception points to a lack of knowledge of climatic requirements for immature development of C. imicola. The absence of C. imicola from the three most easterly sites, which have apparently favourable climates, suggests a relatively recent invasion by this species into Iberia.