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1.
Eur J Intern Med ; 2024 06 12.
Article in English | MEDLINE | ID: mdl-38871565

ABSTRACT

BACKGROUND: In patients complaining common symptoms such as chest/abdominal/back pain or syncope, acute aortic syndromes (AAS) are rare underlying causes. AAS diagnosis requires urgent advanced aortic imaging (AAI), mostly computed tomography angiography. However, patient selection for AAI poses conflicting risks of misdiagnosis and overtesting. OBJECTIVES: We assessed the safety and efficiency of a diagnostic protocol integrating clinical data with point-of-care ultrasound (POCUS) and d-dimer (single/age-adjusted cutoff), to select patients for AAI. METHODS: This prospective study involved 12 Emergency Departments from 5 countries. POCUS findings were integrated with a guideline-compliant clinical score, to define the integrated pre-test probability (iPTP) of AAS. If iPTP was high, urgent AAI was requested. If iPTP was low and d-dimer was negative, AAS was ruled out. Patients were followed for 30 days, to adjudicate outcomes. RESULTS: Within 1979 enrolled patients, 176 (9 %) had an AAS. POCUS led to net reclassification improvement of 20 % (24 %/-4 % for events/non-events, P < 0.001) over clinical score alone. Median time to AAS diagnosis was 60 min if POCUS was positive vs 118 if negative (P = 0.042). Within 941 patients satisfying rule-out criteria, the 30-day incidence of AAS was 0 % (95 % CI, 0-0.41 %); without POCUS, 2 AAS were potentially missed. Protocol rule-out efficiency was 48 % (95 % CI, 46-50 %) and AAI was averted in 41 % of patients. Using age-adjusted d-dimer, rule-out efficiency was 54 % (difference 6 %, 95 % CI, 4-9 %, vs standard cutoff). CONCLUSIONS: The integrated algorithm allowed rapid triage of high-probability patients, while providing safe and efficient rule-out of AAS. Age-adjusted d-dimer maximized efficiency. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04430400.

2.
Chembiochem ; 25(13): e202300863, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38713151

ABSTRACT

Recent advances in bioeconomy allow a holistic view of existing and new process chains and enable novel production routines continuously advanced by academia and industry. All this progress benefits from a growing number of prediction tools that have found their way into the field. For example, automated genome annotations, tools for building model structures of proteins, and structural protein prediction methods such as AlphaFold2TM or RoseTTAFold have gained popularity in recent years. Recently, it has become apparent that more and more AI-based tools are being developed and used for biocatalysis and biotechnology. This is an excellent opportunity for academia and industry to accelerate advancements in the field further. Biotechnology, as a rapidly growing interdisciplinary field, stands to benefit greatly from these developments.


Subject(s)
Biotechnology , Proteins/chemistry , Proteins/metabolism , Biocatalysis , Artificial Intelligence
3.
Infection ; 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38441730

ABSTRACT

PURPOSE: Blood cultures (BCs) are key for pathogen detection in septic patients. We investigated the extent to which sampling was performed and what factors were associated with the absence of general or inadequate BC sampling. METHODS: We conducted a retrospective cohort study of hospitalized patients with sepsis admitted to one of three EDs in 2018. Primary outcome was the extent of general BC collection of at least 1 set. Secondary outcome was the extent of adequate BC sampling, defined as ≥ 2 sets before antibiotic therapy (AT). Multivariable logistic regression analysis was performed to identify factors associated with deficits in both outcomes. RESULTS: 1143 patients were analyzed. BCs were collected from 946 patients. Single BCs were taken from 520 patients, ≥ 2 sets from 426 patients. Overall, ≥ 2 BCs were taken from 349 patients before AT. BC sampling before AT occurred significantly more frequently when ≥ 2 BC sets were taken rather than a single one (81.9%, versus 68.4%, p < 0.001) and this also led to the highest pathogen detection rate in our cohort (65.6%). A body temperature of ≥ 38 °C was the a supporting factor for general and adequate BC collection in all three EDs. Retrospective analysis of 533 patients showed that the qSOFA score had no influence on general or adequate BC collection. CONCLUSION: Data on everyday clinical practice in the pre-analytical phase of microbiological diagnostics shows considerable deficits and indicates the need for more implementation of best practice. The variations identified in BC sampling between EDs should be further investigated.

4.
Acta Paediatr ; 113(4): 684-691, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38226419

ABSTRACT

AIM: The effect of different neonatal unit access hour policies on parental visiting duration is unknown. Therefore, we analysed the effects of access hours policies and parental education on parental visiting duration. METHOD: This prospective longitudinal cohort study was carried out in a level III neonatal unit from October 2020 to May 2022. Three cohorts were compared. The baseline cohort included 51 preterm infants with restricted visiting hours (October 2020 to May 2021). Cohort 1 comprised 35 preterm infants after liberalisation of visiting hours (June 2021 to November 2021). Cohort 2 consisted of 26 preterm infants after an educational program was implemented (December 2021 to May 2022). The primary outcome was the mean daily parental visiting duration. RESULTS: Mean maternal visiting duration was 172 (standard deviation, SD ± 49.2), 195 (SD ± 64.4.), and 258 (SD ± 71.1) minutes/day at baseline and in cohorts 1 and 2 (significant increase from baseline and cohort 1 to cohort 2, p < 0.001). Mean paternal visiting duration did not change significantly across the cohorts: 133 (SD ± 47.2), 135 (SD ± 83.5), and 165 (SD ± 71.3) minutes/day. CONCLUSION: Liberalisation of access hours did not increase parental visiting duration. Parental and staff education significantly increased maternal but not paternal visiting duration.


Subject(s)
Infant, Premature , Parents , Male , Infant , Infant, Newborn , Humans , Prospective Studies , Longitudinal Studies , Policy , Fathers
5.
Epilepsia ; 65(1): 115-126, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37846648

ABSTRACT

OBJECTIVE: The aim was to investigate the monitoring, interventions, and occurrence of critical, potentially life-threatening incidents in patients with Dravet syndrome (DS) and caregivers' knowledge about sudden unexpected death in epilepsy (SUDEP). METHODS: This multicenter, cross-sectional study of patients with DS and their caregivers in Germany consisted of a questionnaire and prospective diary querying the disease characteristics and demographic data of patients and caregivers. RESULTS: Our analysis included 108 questionnaires and 82 diaries. Patients with DS were 49.1% male (n = 53), with a mean age of 13.5 (SD ± 10.0 years) and primary caregivers were 92.6% (n = 100) female, with a mean age of 44.7 (SD ± 10.6 years). Monitoring devices were used regularly by 75.9% (n = 82) of caregivers, and most monitored daily/nightly. Frequently used devices were pulse oximeters (64.6%), baby monitors (64.6%), thermometers (24.1%), and Epi-Care (26.8%). Younger caregiver and patient age and history of status epilepticus were associated with increased use of monitoring, and 81% of monitor users reported having avoided a critical incident with nocturnal monitoring. The need for resuscitation due to cardiac or respiratory arrest was reported by 22 caregivers (20.4%), and most cases (72.7%) were associated with a seizure. Caregivers reported frequently performing interventions at night, including oropharyngeal suction, oxygenation, personal hygiene, and change of body position. Most caregivers were well informed about SUDEP (n = 102; 94%) and monitored for a lateral or supine body position; however, only 39.8% reported receiving resuscitation training, whereas 52.8% (n = 57) knew what to do in case the child's breathing or heart activity failed. SIGNIFICANCE: Critical incidents and the need for resuscitation are reported frequently by caregivers and may be related to high mortality and SUDEP rates in DS. Resuscitation training is welcomed by caregivers and should be continuously provided. Oxygen monitoring devices are frequently used and considered useful by caregivers.


Subject(s)
Epilepsies, Myoclonic , Sudden Unexpected Death in Epilepsy , Child , Humans , Male , Female , Adolescent , Adult , Caregivers , Prospective Studies , Cross-Sectional Studies , Death, Sudden/epidemiology , Death, Sudden/etiology , Epilepsies, Myoclonic/therapy , Germany/epidemiology
6.
Clin Biomech (Bristol, Avon) ; 109: 106079, 2023 10.
Article in English | MEDLINE | ID: mdl-37651899

ABSTRACT

BACKGROUND: Preparing the medullary space of the femur aims to create an ideal form-fitting of cementless implants to provide sufficient initial stability, which is crucial for osseous integration, ensuring good long-term results. Hammering the implant into the proximal femur creates a press-fit anchoring of the endoprosthesis in the medullary space. Implanting the optimal size of the shaft for best fitting should avoid damage to the bone. Modified acoustic signals in connection with implantation are being detected by surgeons and might be related to the primary stability of the implant. METHODS: This study aims to explore the relationship between frequency sound patterns and the change in stem stability. For this purpose, n = 32 Metha® short stems were implanted in a clinical setting by the same surgeon. During implantation, the sounds were recorded. To define a change in the acoustic system response during the operation, the individual blows of the implantation sequence were correlated with one another. FINDINGS: An algorithm was able to subdivide through sound analysis two groups of hammer blows (area 1 and area 2) since the characteristics of these groups showed significant differences within the frequency range of 100 Hz to 24 kHz. The edge between both groups, detected by the algorithm, was validated with expert surgeons' classifications of the same data. INTERPRETATION: In conclusion, monitoring, the hammer blows sound might allow quantification of the primary stability of the implant. Sound analysis including patient parameters and a classification algorithm could provide a precise characterization of implant stability.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Humans , Arthroplasty, Replacement, Hip/methods , Prosthesis Design , Femur/surgery , Acoustics
7.
J Clin Med ; 12(15)2023 Aug 07.
Article in English | MEDLINE | ID: mdl-37568553

ABSTRACT

Open spina bifida (OSB) is a congenital, non-lethal malformation with multifactorial etiology. Fetal therapy can be offered under certain conditions to parents after accurate prenatal diagnostic and interdisciplinary counseling. Since the advent of prenatal OSB surgery, various modifications of the original surgical techniques have evolved, including laparotomy-assisted fetoscopic repair. After a two-year preparation time, the team at the University of Giessen and Marburg (UKGM) became the first center to provide a three-port, three-layer fetoscopic repair of OSB via a laparotomy-assisted approach in the German-speaking area. We point out that under the guidance of experienced centers and by intensive multidisciplinary preparation and training, a previously described and applied technique could be transferred to a different setting.

8.
BMC Pediatr ; 23(1): 344, 2023 07 07.
Article in English | MEDLINE | ID: mdl-37420180

ABSTRACT

BACKGROUND: The therapeutic advances and progress in the care for preterm infants have enabled the regular survival of very immature infants. However, the high burden of lifelong sequelae following premature delivery constitutes an ongoing challenge. Regardless of premature delivery, parental mental health and a healthy parent-child relationship were identified as essential prerogatives for normal infant development. Family centered care (FCC) supports preterm infants and their families by respecting the particular developmental, social and emotional needs in the Neonatal Intensive Care Unit. Due to the large variations in concepts and goals of different FCC initiatives, scientific data on the benefits of FCC for the infant and family outcome are sparse and its effects on the clinical team need to be elaborated. METHODS: This prospective single centre longitudinal cohort study enrols preterm infants ≤ 32 + 0 weeks of gestation and/or birthweight ≤ 1500 g and their parents at the neonatal department of the Giessen University Hospital, Giessen, Germany. Following a baseline period, the rollout of additional FCC elements is executed following a stepwise 6-months approach that covers the NICU environment, staff training, parental education and psychosocial support for parents. Recruitment is scheduled over a 5.5. year period from October 2020 to March 2026. The primary outcome is corrected gestational age at discharge. Secondary infant outcomes include neonatal morbidities, growth, and psychomotor development up to 24 months. Parental outcome measures are directed towards parental skills and satisfaction, parent-infant-interaction and mental health. Staff issues are elaborated with particular focus on the item workplace satisfaction. Quality improvement steps are monitored using the Plan- Do- Study- Act cycle method and outcome measures cover the infant, the parents and the medical team. The parallel data collection enables to study the interrelation between these three important areas of research. Sample size calculation was based on the primary outcome. DISCUSSION: It is scientifically impossible to allocate improvements in outcome measures to individual enhancement steps of FCC that constitutes a continuous change in NICU culture and attitudes covering diverse areas of change. Therefore, our trial is designed to allocate childhood, parental and staff outcome measures during the stepwise changes introduced by a FCC intervention program. TRIAL REGISTRATION: Clinicaltrials.gov, trial registration number NCT05286983, date of registration 03/18/2022, retrospectively registered, http://clinicaltrials.gov .


Subject(s)
Intensive Care Units, Neonatal , Premature Birth , Female , Infant, Newborn , Infant , Humans , Child , Infant, Premature , Longitudinal Studies , Prospective Studies , Parents/psychology , Cohort Studies , Patient-Centered Care
9.
Orphanet J Rare Dis ; 18(1): 98, 2023 04 29.
Article in English | MEDLINE | ID: mdl-37120555

ABSTRACT

BACKGROUND: This study measured sleep quality among caregivers of patients with Dravet syndrome (DS) and assessed the impacts of mental health problems and caregiver burden on sleep quality. METHODS: This multicenter, cross-sectional study of patients with DS and their caregivers throughout Germany consisted of a questionnaire and a prospective 4-week diary querying disease characteristics, demographic data, living conditions, nocturnal supervision, and caregivers' work situations. Sleep quality was assessed using the Pittsburgh Sleeping Quality Index (PSQI). The Hospital Anxiety and Depression Scale (HADS) and the Burden Scale for Family Caregivers (BSFC) were used to measure anxiety, symptoms of depression, and caregiver burden. RESULTS: Our analysis included 108 questionnaires and 82 four-week diaries. Patients with DS were 49.1% male (n = 53), with a mean age of 13.5 ± 10.0 years. Caregivers were 92.6% (n = 100) female, with a mean age of 44.7 ± 10.6 years. The overall mean PSQI score was 8.7 ± 3.5, with 76.9% of participants (n = 83) scoring 6 or higher, indicating abnormal sleep quality. The HADS for anxiety and depression had overall mean scores of 9.3 ± 4.3 and 7.9 ± 3.7, respectively; 61.8% and 50.9% of participants scored above the cutoff value of 8 for anxiety and depression, respectively. Statistical analyses revealed caregiver anxiety levels and patients' sleep disturbances as major factors influencing PSQI scores. The overall mean BSFC score of 41.7 ± 11.7 indicates a moderate burden, with 45.3% of caregivers scoring 42 or higher. CONCLUSIONS: Sleep quality is severely affected among caregivers of patients with DS, correlating with anxiety, comorbidities, and patients' sleep disturbances. A holistic therapeutic approach should be implemented for patients with DS and their caregivers, focusing on the sleep quality and mental health of caregivers. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00016967. Registered 27 May 2019, http://www.drks.de/DRKS00016967.


Subject(s)
Epilepsies, Myoclonic , Sleep Wake Disorders , Humans , Male , Female , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Quality of Life/psychology , Caregiver Burden , Sleep Quality , Depression/psychology , Cross-Sectional Studies , Prospective Studies , Anxiety , Caregivers/psychology , Surveys and Questionnaires , Germany , Patient Care
10.
Med Eng Phys ; 111: 103932, 2023 01.
Article in English | MEDLINE | ID: mdl-36792236

ABSTRACT

Aseptic loosening is a frequent cause for revision of endoprosthesis. X-ray examinations like Radio-Stereometry-Analysis (RSA) are among the most widely used in vivo methods for its detection. Nevertheless, this method is not used routinely because of bone marker and related radiation exposure. This work aims at creating a new in vivo concept to detect implant stability measuring micromotions without x-ray and to develop a corresponding algorithm. Based on the assumption of contactless measurement, the input parameters for the algorithm are the distances of each ultrasound sensor to the object (prosthesis and bone) and its position. First, the number of parameters necessary for a precise reconstruction and measurement of micromotions between objects had to be defined. Therefore, the algorithm has been tested with simulations of these parameters. Two experimental measurements, either using contact sensors or ultrasound, were used to prove the accuracy of the algorithm. Simulations indicate a high accuracy with three distances as initial parameters for each object. Contact measurements show precise representation of micromotion, and the contactless measurements show the possibility of detecting various materials with a high resolution. This work lays the foundations for non-invasive detection of micromotions between the implant-bone interface.


Subject(s)
Hip Prosthesis , Prosthesis Design , Bone and Bones
12.
Phys Rev Lett ; 130(4): 041901, 2023 Jan 27.
Article in English | MEDLINE | ID: mdl-36763443

ABSTRACT

We study the associated production of prompt J/ψ mesons and W or Z bosons within the factorization approach of nonrelativistic QCD (NRQCD) at next-to-leading order in α_{s}, via intermediate color singlet ^{3}S_{1}^{[1]} and ^{3}P_{J}^{[1]} and color octet ^{1}S_{0}^{[8]}, ^{3}S_{1}^{[8]}, and ^{3}P_{J}^{[8]} states. Requiring for our predictions to be compatible with recent ATLAS measurements yields stringent new constraints on charmonium long-distance matrix elements (LDMEs) being nonperturbative, process-independent input parameters. Considering four popular LDME sets fitted to data of single J/ψ inclusive production, we find that one is marginally compatible with the data, with central predictions typically falling short by a factor of 3, one is unfavored, the factor of shortfall being about 1 order of magnitude, and two violate cross section positivity for direct J/ψ+W/Z production. The large rate of prompt J/ψ plus W production observed by ATLAS provides strong evidence for the color octet mechanism inherent to NRQCD factorization, the leading color singlet contribution entering only at O(G_{F}α_{s}^{4}), beyond the order considered here.

13.
Article in English | MEDLINE | ID: mdl-36282483

ABSTRACT

BACKGROUND: Paediatric hydrocephalus is a result of a dysfunction of cerebrospinal fluid circulation, and it has diverse pathogeneses. This study investigates the epidemiology of paediatric hydrocephalus, as well as the influences of primary aetiology and implant type on treatment complications and the development of new therapeutic approaches and strategies. METHODS: Between 2013 and 2018, a retrospective analysis of 131 children, who were suffering from hydrocephalus, was conducted. Medical charts, operative reports and clinical follow-up visits were reviewed. Statistical analysis was performed using t-test/ANOVA and Kruskal-Wallis test/Mann-Whitney U test. RESULTS: The most common pathogeneses of hydrocephalus among our patients were meningomyelocele-associated and posthaemorrhagic. The majority of patients received a programmable differential pressure valve (PPV, 77.8%) or a fixed differential pressure valve with a gravitational unit (FPgV, 14.8%). Among 333 shunt-associated surgeries, 66% of surgeries were revision surgeries and were performed because of mechanical shunt dysfunction (61%), infection (12%), or other reasons (27%). The median rate of revisions within one year for each patient was 0.15 (IQR25-75: 0.00-0.68) and was influenced by aetiology (p = 0.045) and valve type (p = 0.029). The highest rates were seen in patients with posthaemorrhagic hydrocephalus and in those with FPgVs; the lowest rates were seen in patients with meningomyelocele-associated hydrocephalus and PPVs. The occurrence of mechanical dysfunctions was correlated with FPgV patients (p = 0.014). Furthermore, the median time interval between initial shunt surgery and onset of infection was shorter than that between initial surgery and mechanical dysfunction (p = 0.033). CONCLUSIONS: Based on this research, we can state several factors that influence revision surgeries in paediatric shunt patients. With the assessment of patients' risk profiles, physicians can classify paediatric shunt patients and thus avoid unnecessary examinations or invasive procedures. Furthermore, medical providers can prevent revision surgeries if they choose shunt material in accordance with a patient's associated shunt complications.

14.
Neurol Res Pract ; 4(1): 22, 2022 Jun 06.
Article in English | MEDLINE | ID: mdl-35659154

ABSTRACT

BACKGROUND: In Dravet syndrome (DS), a rare epileptic and developmental encephalopathy, the effectiveness of a new treatment is predominantly measured in terms of seizure frequency. However, this may not fully capture the impact of a treatment on the broader aspects of the syndrome and patients' health-related quality of life (HRQoL). Using a previously published survey which collected data from DS patients and their carers on the broader manifestations of their syndrome, their HRQoL, and their experience of seizures, this study created composite measures of symptom severity to offer new perspectives on the multifaceted aspects of this rare condition. METHODS: Survey responses on the severity of physical and psychosocial symptoms were combined with independent assessments of disability and care need, to generate three composite symptom scores assessing the manifestations of DS (physical, psychosocial and care requirements). Variation in HRQoL was investigated in multiple regression analyses to assess the strength of association between each of these composite measures and three forms of seizure measures (seizure frequency, days with no seizures and longest interval without seizures), as experienced over a 4- and 12-week period. RESULTS: Composite scores were calculated for a cohort of 75 primarily paediatric patients who were enrolled in the study. Strong associations were found between each of the three composite symptom scores and each of the three seizure measures, with the regression coefficient on symptom score highly significant (p ≤ 0.001) in all nine comparisons. Separate regressions using predictors of HRQoL (Kiddy KINDL and Kid KINDL) as the dependent variable were inconclusive, identifying only behavioural/attention problems and status epilepticus as significant predictors of HRQoL. CONCLUSIONS: These results allow the development of a composite score that may be useful in developing a clinical understanding of the severity of DS for an individual patient and establishing their treatment goals. Where measurement of long-term sequalae of disease is not feasible, such as clinical trials, correlation of the composite score with experience of seizures and seizure-free periods may allow a better contextualisation of the results of short-term assessments. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00011894. Registered 16 March 2017, http://www.drks.de/ DRKS00011894.

15.
Front Psychol ; 13: 836695, 2022.
Article in English | MEDLINE | ID: mdl-35496154

ABSTRACT

Background: Resistance training (RT) can offer beneficial physiological and psychological effects. The regular continuation of this exercise can be accomplished by improving the recovery and mood after a workout. Frequency-specific microcurrent (microstimulation) might offer a solution here as it has been shown to improve physical injuries, mood state, and sleep. However, knowledge is lacking about the impact of microstimulation after RT on said parameters. The present study aimed to test the effects of RT and muscle-microstimulation on mood and physical recovery in healthy men after performing conventional deadlifts, which is a type of RT. Methods: The study was conducted according to a single-blind, randomized, placebo-controlled, and two-way crossover study. Twenty participants naïve to microstimulation (MS) engaged in RT twice on separate days. They were randomized to receive MS on 1 day and no microstimulation (Sham-MS) on another day. Before and after the workout and after their treatment (MS or Sham-MS), participants self-rated their mood state and mental and physical exhaustion levels. Results: Findings showed that MS increased the self-ratings of well-rested and sociable and, most importantly, reduced the feeling of exercise-induced exhaustion. There were no MS effects on ratings of feeling sad, happy, or exhausted, although the workout, independent of MS, negatively influenced the level of exhaustion. Conclusion: The combination of enhanced sociableness, reduced fatigue, and exercise-induced exhaustion after a workout, followed by microstimulation, has important implications for professional sporters and nonprofessionals who try to get the best result after a workout. Future studies using a double-blind approach including different types of exercises, different durations of programs, and both sexes can shed more light on the full potential of microstimulation after a workout on mood state and exercise-induced exhaustion.

16.
Neuropediatrics ; 53(1): 39-45, 2022 02.
Article in English | MEDLINE | ID: mdl-34852371

ABSTRACT

Little is known about clinical symptomatology and genetics of juvenile onset Pompe disease (JOPD). The aims of this study were to analyze how these children are diagnosed, what clinical problems they have, and how phenotype is related to genotype. To accomplish this, we analyzed retrospectively data of 34 patients diagnosed after their first and before completion of their 18th birthday. Median age at diagnosis was 3.9 (range 1.1-17) years. Eight patients (23.5%) developed initial symptoms in the first year, 12 (35%) between 1 and 7 years, and 6 (18%) thereafter. Eight (23.5%) had no clinical symptoms at the time of diagnosis. Indications for diagnostics were a positive family history in three (9%), hyperCKemia in eight (23.5%), motor developmental delay in three (9%), and muscle weakness and/or pain in 17 (50%). Rare clinical signs were failure to thrive, recurrent diarrhea, and suspected hepatopathy with glycogen storage. Thirty-two different mutations were identified. Twenty-seven patients (79.5%) carried the milder c.32-13T > G mutation, known to be associated with a broad range of phenotypes. Three out of eight patients manifesting within the first year of life showed generalized muscle weakness, hypertrophic cardiomyopathy, and had to be ventilated during the course of disease, thereby demonstrating clinical overlap with infantile onset Pompe disease.These findings demonstrate that the phenotype of JOPD is broad and that the differential is not only restricted to neuromuscular disorders. Genotypic analysis was useful to delineate subjects with early onset JOPD from those with IOPD, but overall genotype-phenotype correlation was poor.


Subject(s)
Glycogen Storage Disease Type II , Glycogen Storage Disease Type II/diagnosis , Glycogen Storage Disease Type II/genetics , Humans , Mutation , Phenotype , Retrospective Studies , alpha-Glucosidases/genetics
17.
Phys Chem Chem Phys ; 24(2): 941-954, 2022 Jan 04.
Article in English | MEDLINE | ID: mdl-34913940

ABSTRACT

We present a combined experimental and theoretical study of the fragmentation of singly and doubly N-methylated glycine (sarcosine and N,N-dimethyl glycine, respectively) induced by low-energy (keV) O6+ ions. Multicoincidence mass spectrometry techniques and quantum chemistry simulations (ab initio molecular dynamics and density functional theory) allow us to characterise different fragmentation pathways as well as the associated mechanisms. We focus on the fragmentation of doubly ionised species, for which coincidence measurements provide unambiguous information on the origin of the various charged fragments. We have found that single N-methylation leads to a larger variety of fragmentation channels than in no methylation of glycine, while double N-methylation effectively closes many of these fragmentation channels, including some of those appearing in pristine glycine. Importantly, the closure of fragmentation channels in the latter case does not imply a protective effect by the methyl group.


Subject(s)
Glycine/chemistry , Sarcosine/chemistry , Density Functional Theory , Glycine/analogs & derivatives , Ions , Methylation , Molecular Dynamics Simulation
19.
Ger Med Sci ; 19: Doc13, 2021.
Article in English | MEDLINE | ID: mdl-34867135

ABSTRACT

Carbon monoxide (CO) can occur in numerous situations and ambient conditions, such as fire smoke, indoor fireplaces, silos containing large quantities of wood pellets, engine exhaust fumes, and when using hookahs. Symptoms of CO poisoning are nonspecific and can range from dizziness, headache, and angina pectoris to unconsciousness and death. This guideline presents the current state of knowledge and national recommendations on the diagnosis and treatment of patients with CO poisoning. The diagnosis of CO poisoning is based on clinical symptoms and proven or probable exposure to CO. Negative carboxyhemoglobin (COHb) levels should not rule out CO poisoning if the history and symptoms are consistent with this phenomenon. Reduced oxygen-carrying capacity, impairment of the cellular respiratory chain, and immunomodulatory processes may result in myocardial and central nervous tissue damage even after a reduction in COHb. If CO poisoning is suspected, 100% oxygen breathing should be immediately initiated in the prehospital setting. Clinical symptoms do not correlate with COHb elimination from the blood; therefore, COHb monitoring alone is unsuitable for treatment management. Especially in the absence of improvement despite treatment, a reevaluation for other possible differential diagnoses ought to be performed. Evidence regarding the benefit of hyperbaric oxygen therapy (HBOT) is scant and the subject of controversy due to the heterogeneity of studies. If required, HBOT should be initiated within 6 h. All patients with CO poisoning should be informed about the risk of delayed neurological sequelae (DNS).


Subject(s)
Carbon Monoxide Poisoning , Hyperbaric Oxygenation , Carbon Monoxide Poisoning/diagnosis , Carbon Monoxide Poisoning/therapy , Carboxyhemoglobin , Dizziness , Humans , Oxygen
20.
Sci Adv ; 7(40): eabg9080, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34597129

ABSTRACT

The way molecules break after ion bombardment is intimately related to the early electron dynamics generated in the system, in particular, charge (or electron) migration. We exploit the natural positive-negative charge splitting in the zwitterionic molecule betaine to selectively induce double electron removal from its negatively charged side by impact of fast O6+ ions. The loss of two electrons in this localized region of the molecular skeleton triggers a competition between direct Coulomb explosion and charge migration that is examined to obtain temporal information from ion-ion coincident measurements and nonadiabatic molecular dynamics calculations. We find a charge migration time, from one end of the molecule to the other, of approximately 20 to 40 femtoseconds. This migration time is longer than that observed in molecules irradiated by ultrashort light pulses and is the consequence of charge migration being driven by adiabatic nuclear dynamics in the ground state of the molecular dication.

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