Abstract
We measured the mid-infrared (MIR) extinction using Spitzer photometry and spectroscopy (3.6–37
μ
m) for a sample of Milky Way sight lines (mostly) having measured ultraviolet extinction ...curves. We used the pair method to determine the MIR extinction that we then fit with a power law for the continuum and modified Drude profiles for the silicate features. We derived 16 extinction curves having a range of
A
(
V
) (1.8–5.5) and
R
(
V
) values (2.4–4.3). Our sample includes two dense sight lines that have 3
μ
m ice feature detections and weak 2175 Å bumps. The average
A
(
λ
)/
A
(
V
) diffuse sight-line extinction curve we calculate is lower than most previous literature measurements. This agrees better with literature diffuse dust grain models, though it is somewhat higher. The 10
μ
m silicate feature does not correlate with the 2175 Å bump, for the first time providing direct observational confirmation that these two features arise from different grain populations. The strength of the 10
μ
m silicate feature varies by ∼2.5 and is not correlated with
A
(
V
) or
R
(
V
). It is well fit by a modified Drude profile with strong correlations seen between the central wavelength, width, and asymmetry. We do not detect other features with limits in
A
(
λ
)/
A
(
V
) units of 0.0026 (5–10
μ
m), 0.004 (10–20
μ
m), and 0.008 (20–40
μ
m). We find that the standard prescription of estimating
R
(
V
) from
C
×
E
(
K
s
−
V
)/
E
(
B
−
V
) has
C
= −1.14 and a scatter of ∼7%. Using the IRAC 5.6
μ
m band instead of
K
s
gives
C
= −1.03 and the least scatter of ∼3%.
The PI3K‐AKT signalling cascade has a highly conserved role in a variety of processes including cell growth and glucose homoeostasis. Variants affecting this pathway can lead to one of several ...segmental overgrowth disorders. These conditions are genetically heterogeneous and require tailored, multidisciplinary involvement throughout life. Hypoglycaemia is common in other overgrowth syndromes but has been described only sporadically in association with PIK3CA and CCND2 variants. We report a cohort of 6 children with megalencephaly‐capillary malformation (MCAP) and megalencephaly‐polydactyly‐polymicrogyria‐hydrocephalus (MPPH) syndromes who developed clinically significant hypoglycaemia. Based on our findings, we suggest that segmental overgrowth patients should be screened for low blood glucose levels during childhood and there should be early specialist endocrine review in any children who develop hypoglycaemia.
We report a cohort of 6 children with segmental overgrowth (MCAP and MPPH) who developed clinically significant hypoglycaemia.
Perrault syndrome is a genetically and clinically heterogeneous autosomal-recessive condition characterized by sensorineural hearing loss and ovarian failure. By a combination of linkage analysis, ...homozygosity mapping, and exome sequencing in three families, we identified mutations in CLPP as the likely cause of this phenotype. In each family, affected individuals were homozygous for a different pathogenic CLPP allele: c.433A>C (p.Thr145Pro), c.440G>C (p.Cys147Ser), or an experimentally demonstrated splice-donor-site mutation, c.270+4A>G. CLPP, a component of a mitochondrial ATP-dependent proteolytic complex, is a highly conserved endopeptidase encoded by CLPP and forms an element of the evolutionarily ancient mitochondrial unfolded-protein response (UPRmt) stress signaling pathway. Crystal-structure modeling suggests that both substitutions would alter the structure of the CLPP barrel chamber that captures unfolded proteins and exposes them to proteolysis. Together with the previous identification of mutations in HARS2, encoding mitochondrial histidyl-tRNA synthetase, mutations in CLPP expose dysfunction of mitochondrial protein homeostasis as a cause of Perrault syndrome.
Angelman syndrome ( AS) is a neurodevelopmental disorder characterised by severe learning difficulties, ataxia, a seizure disorder with a characteristic EEG, subtle dysmorphic facial features, and a ...happy, sociable disposition. Most children present with delay in developmental milestones and slowing of head growth during the first year of life. In the majority of cases speech does not develop. Patients with AS have a characteristic behavioural phenotype with jerky movements, frequent and sometimes inappropriate laughter, a love of water, and sleep disorder. The facial features are subtle and include a wide, smiling mouth, prominent chin, and deep set eyes. It is caused by a variety of genetic abnormalities involving the chromosome 15q11-13 region, which is subject to genomic imprinting. These include maternal deletion, paternal uniparental disomy, imprinting defects, and point mutations or small deletions within the UBE3A gene, which lies within this region. UBE3A shows tissue specific imprinting, being expressed exclusively from the maternal allele in brain. The genetic mechanisms identified so far in AS are found in 85-90% of those with the clinical phenotype and all interfere with UBE3A expression.
The Mariana Trench is the deepest known site in the Earth's oceans, reaching a depth of ~ 11,000 m at the Challenger Deep. Recent studies reveal that hadal waters harbor distinctive microbial ...planktonic communities. However, the genetic potential of microbial communities within the hadal zone is poorly understood.
Here, implementing both culture-dependent and culture-independent methods, we perform extensive analysis of microbial populations and their genetic potential at different depths in the Mariana Trench. Unexpectedly, we observed an abrupt increase in the abundance of hydrocarbon-degrading bacteria at depths > 10,400 m in the Challenger Deep. Indeed, the proportion of hydrocarbon-degrading bacteria at > 10,400 m is the highest observed in any natural environment on Earth. These bacteria were mainly Oleibacter, Thalassolituus, and Alcanivorax genera, all of which include species known to consume aliphatic hydrocarbons. This community shift towards hydrocarbon degraders was accompanied by increased abundance and transcription of genes involved in alkane degradation. Correspondingly, three Alcanivorax species that were isolated from 10,400 m water supplemented with hexadecane were able to efficiently degrade n-alkanes under conditions simulating the deep sea, as did a reference Oleibacter strain cultured at atmospheric pressure. Abundant n-alkanes were observed in sinking particles at 2000, 4000, and 6000 m (averaged 23.5 μg/gdw) and hadal surface sediments at depths of 10,908, 10,909, and 10,911 m (averaged 2.3 μg/gdw). The δ
H values of n-C
alkanes that dominated surface sediments at near 11,000-m depths ranged from - 79 to - 93‰, suggesting that these sedimentary alkanes may have been derived from an unknown heterotrophic source.
These results reveal that hydrocarbon-degrading microorganisms are present in great abundance in the deepest seawater on Earth and shed a new light on potential biological processes in this extreme environment.
We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European ...mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (χ2 test: P = 2.12 × 10−51; Fisher's exact test: heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9-11.3), and homozygote OR = 151 (95% c.i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles.
Intrabolus pressure (IBP) recorded by high-resolution manometry (HRM) portrays the compartmentalized force on a bolus during esophageal peristalsis. HRM may be a reliable screening tool for ...esophageal dysmotility in patients with elevated average maximum IBP (AM-IBP). Timed barium esophagram (TBE) is a validated measure of esophageal emptying disorders, such as esophagogastric junction outflow obstruction and achalasia. This study aimed to determine if an elevated AM-IBP correlates with esophageal dysmotility on HRM and/or delayed esophageal emptying on TBE.
A retrospective analysis of all HRM (unweighted sample n = 155) performed at a tertiary referral center from 09/2015-03/2017 yielded a case group (n = 114) with abnormal AM-IBP and a control group (n = 41) with a normal AM-IBP (pressure < 17 mmHg) as consistent with Chicago Classification 3. All patients received a standardized TBE, with abnormalities classified as greater than 1 cm of retained residual liquid barium in the esophagus at 1 and 5 min or as tablet retention after 5 min.
AM-IBP was significantly related to liquid barium retention (p = 0.003) and tablet arrest on timed barium esophagram (p = 0.011). A logistic regression model correctly predicted tablet arrest in 63% of cases. Tablet arrest on AM-IBP correlated with an optimal prediction point at 20.1 mmHg on HRM. Patients with elevated AM-IBP were more likely to have underlying esophageal dysmotility (95.6% vs. 70.7% respectively; p < 0.001), particularly esophagogastric junction outflow obstruction disorders. Elevated AM-IBP was associated with incomplete liquid bolus transit on impedance analysis (p = 0.002).
Our findings demonstrate that an elevated AM-IBP is associated with abnormal TBE findings of esophageal tablet retention and/or bolus stasis. An abnormal AM-IBP (greater than 20.1 mm Hg) was associated with a higher probability of retaining liquid bolus or barium tablet arrest on TBE and esophageal dysmotility on HRM. This finding supports the recent incorporation of IBP in Chicago Classification v4.0.
Abstract Background The analysis of the different operative reconstructions of patellar tendon ruptures has not been reported. A critical review of the existing literature was performed to identify ...the different operative techniques and the post-operative outcomes in acute, chronic and post-total knee arthroplasty (TKA) patellar tendon rupture repairs. Methods Using PRISMA guidelines, a review of the English-written literature published after 1947 was performed using the MEDLINE, PubMed and Cochrane libraries in November 2013 to retrieve case series with the keywords “Patellar tendon” AND “Rupture” AND “Repair” in their title or abstract. Results Forty-one manuscripts, reporting on 503 patients were analysed. Three-hundred-and-fifty-four acute repairs described eight different operative techniques. One-hundred-and-forty-nine chronic repairs described eight different operative techniques. Sixty-eight post-TKA repairs described nine different operative techniques. Six acute, four chronic and seven post-TKA repair operative techniques reported failures. In acute repair, using a primary repair method augmented with cerclage wire, Dall–Miles cable or non-absorbable sutures reported the best clinical results, with a 2% failure rate. Alternatively, for chronic and post-TKA repair, autogeneous grafts were significantly better than primary repair (p = 0.0252, 0.0038 respectively). Conclusion Acute surgical repair of a patellar tendon rupture using augmented primary repair is associated with the best post-operative outcomes. In chronic and post-TKA repair, autogeneous grafts produce best post-operative outcomes. Immediate post-operative mobilisation should be considered in all repairs. Future papers reporting on patellar operative repairs should have a standardised scoring method of functional outcome to allow more comprehensive comparison and evaluation.
Category:
Ankle; Hindfoot
Introduction/Purpose:
Tibiotalocalcaneal (TTC) arthrodesis is a treatment option for several pathologies of the hindfoot and ankle. Traditional fixation options include ...intramedullary nailing or plate-screw constructs. In certain patients, for example when bone quality or post-operative compliance are of concern, more robust fixation may be desired. Charcot neuroarthropathy (CN) patients in particular often have complex deformities, poor bone quality, and impaired sensation. New trauma literature shows hybrid nail-plate constructs (NPCs) may permit early weight bearing in osteoporotic distal femur fractures. We report early results of TTC arthrodesis using NPCs in patients with complex deformities of the ankle and hindfoot.
Methods:
Patients undergoing TTC arthrodesis via intramedullary nail fixation plus plating by a single surgeon from September 2020 to December 2022 were included in our study. Indications included CN, post-traumatic deformities, and advanced arthritis. Age, comorbidities, Hemoglobin A1c, presence of an ulcer, implants, bone graft used, and postoperative complications were retrospectively recorded.
Results:
Fifteen patients met inclusion criteria. Six patients had CN; eight patients had post-traumatic complications; and one patient had an arthritic cavovarus deformity. Average age was 55 years (range 31-72). Eleven patients were treated with a lateral TTC locking plate; three were treated with an anterior tibiotalar arthrodesis plate; and one was treated with a 3.5mm reconstruction plate. All patients were treated with a TTC arthrodesis nail. In all cases, cellular bone matrix was used; in fourteen cases, autograft was also used. Average follow-up was 35 weeks (min. 12). Three patients underwent below-knee amputation, two for infection and the other for hardware failure. Two others required postoperative debridements but subsequently cleared their infections. Twelve patients have a stable, non-infected, ulcer free foot at latest follow-up.
Conclusion:
TTC arthrodesis can be used for a variety of indications, and many of these patients present complex challenges. Patients with CN in particular often have severe deformities and poor bone quality. Hybrid fixation methods provide added stability in complex cases, possibly allowing for more powerful deformity correction and earlier weight-bearing. We report a 80% favorable outcome rate in our case series, with major complications confined to patients with significant medical comorbidities (poorly controlled diabetes, peripheral vascular disease). We believe that TTC arthrodesis with hybrid nail-plate constructs represents an attractive solution to complex ankle and hindfoot deformities.
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