The existence of natural ice-caves at depths varying from 50 to 200 feet below the surface of the earth, unconnected with glaciers or snow mountains, and in latitudes and at altitudes where ice could ...not under ordinary circumstances be supposed to exist, has attracted some attention. In addition to the description of this natural phenomena, the author has interspersed his incidents of travel. He has also given accounts of similar caves in different parts of the world.
Epidermolysis Bullosa (EB) is a group of rare genetic disorders resulting in skin fragility and other symptoms. Commissioned by DEBRA International and funded by DEBRA Norway, this evidence-bases ...guideline provides recommendations to optimise psychosocial wellbeing in EB.An international multidisciplinary panel of social and health care professionals (HCP) and people living with EB was formed. A systematic international literature review was conducted by the panel following the Scottish Intercollegiate Guidelines Network (SIGN) methodology. The resulting papers underwent systematic selection and critique processes. Included papers were allocated to 6 different outcome groups to allow data synthesis and exploration: quality of life, coping, family, wellbeing, access to HCP and pain. Based on the evidence in those papers, recommendations were made for individuals living with EB, family and caregivers and HCP working in the field.Few studies have investigated interventions and which factors lead to better outcomes, but general recommendations can be made. EB is a complex disease impacting enormously on every aspect of psychosocial life. People and families living with EB need access to multidisciplinary support, including psychological guidance, in order to improve quality of life and psychosocial wellbeing. Interventions should stimulate social participation to prevent isolation. People with EB and their families should be able to access a supportive network. HCP should be well supported and educated about the complexity of EB. They should work collaboratively with those around the individual with EB (e.g. schools, employers etc.) to provide psychosocial opportunity and care.Attention should be paid to the psychosocial impact of EB as well as physical needs. Directions for research are indicated.
Tau neurofibrillary tangles are a hallmark of Alzheimer’s disease neuropathological change. However, it remains largely unclear how distinctive Alzheimer’s disease tau seeds (i.e. 3R/4R) correlate ...with histological indicators of tau accumulation. Furthermore, AD tau co-pathology is thought to influence features and progression of other neurodegenerative diseases including Lewy body disease; yet measurements of different types of tau seeds in the setting of such diseases is an unmet need. Here, we use tau real-time quaking-induced conversion (RT-QuIC) assays to selectively quantitate 3R/4R tau seeds in the frontal lobe which accumulates histologically identifiable tau pathology at late disease stages of AD neuropathologic change. Seed quantitation across a spectrum of neurodegenerative disease cases and controls indicated tau seeding activity can be detected well before accompanying histopathological indication of tau deposits, and even prior to the earliest evidence of Alzheimer’s-related tau accumulation anywhere in the brain. In later stages of AD, 3R/4R tau RT-QuIC measures correlated with immunohistochemical tau burden. In addition, Alzheimer’s tau seeds occur in the vast majority of cases evaluated here inclusive of primary synucleinopathies, frontotemporal lobar degeneration and even controls albeit at multi-log lower levels than Alzheimer’s cases. α-synuclein seeding activity confirmed synucleinopathy cases and further indicated the co-occurrence of α-synuclein seeds in some Alzheimer’s disease and primary tauopathy cases. Our analysis indicates that 3R/4R tau seeds in the mid-frontal lobe correlate with the overall Braak stage and Alzheimer’s disease neuropathologic change, supporting the quantitative predictive value of tau RT-QuIC assays. Our data also indicate 3R/4R tau seeds are elevated in females compared to males at high (≥ IV) Braak stages. This study suggests 3R/4R tau seeds are widespread even prior to the earliest stages of Alzheimer’s disease changes, including in normal, and even young individuals, with prevalence across multiple neurodegenerative diseases to further define disease subtypes.
Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency ...of synaptic transmission. We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease. Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates. Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis. Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Midface toddler excoriation syndrome (MiTES) is a condition recently reported in three unrelated children. Habitual scratching from the first year of life inflicted deep, chronic, ...scarring wounds around the nose and eyes. One child had a mild neurological deficit but there was no other evidence of insensitivity to pain. Bilateral distribution and localization to the midface distinguish MiTES from other causes of self‐inflicted skin damage such as trigeminal trophic syndrome. An earlier study of five siblings from a consanguineous Irish family, with lesions corresponding to MiTES plus other sensory deficits, showed homozygous mutations in a gene for hereditary sensory and autonomic neuropathy type VIII (HSAN8), PRDM12.
Objectives
To study further cases of MiTES, including analysis of PRDM12.
Methods
We describe five further children, from four families, with facial lesions typical of MiTES, in whom mutation analysis of PRDM12 was carried out.
Results
Homozygous or compound heterozygous pathogenic expansions of the PRDM12 polyalanine tract were found in four of five affected individuals, in three families.
Conclusions
Our finding of autosomal recessive mutations in PRDM12 in four of five patients with MiTES extends the phenotypic spectrum of PRDM12 mutations, which usually cause HSAN8, characterized by mutilating self‐inflicted wounds of the extremities, lips and tongue. By contrast, MiTES shows severe midfacial lesions with little if any evidence of generalized pain insensitivity. The condition is probably genetically heterogeneous, and other congenital insensitivity to pain and HSAN genes such as SCN11A may be implicated. This new understanding of the nature of MiTES, which can masquerade as factitious disease, will facilitate appropriate management.
What's already known about this topic?
Midface toddler excoriation syndrome (MiTES) is a newly recognized condition, described in three children, characterized by severe, chronic, scarring, self‐inflicted midface excoriations, commencing in infancy.
MiTES resembles fabricated and induced illness.
The gene PRDM12 is responsible for an autosomal recessive disorder, hereditary sensory and autonomic neuropathy type VIII (HSAN8), characterized by congenital insensitivity to pain with ulceration to the extremities.
A family with mild manifestations of HSAN8 and MiTES lesions had homozygous mutations in PRDM12.
What does this study add?
We report a further five children with MiTES, in four families.
Mutation analysis revealed biallelic mutations in PRDM12 in four children in three families. No mutations were found in the fifth child.
This confirms MiTES as a recessive disorder of pain sensation, which is probably genetically heterogeneous.
This new finding will improve our understanding of children presenting with this condition.
Linked Comment: Greenblatt and Mellerio. Br J Dermatol 2018; 179:1029.
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Transitional cell carcinoma (TCC) accounts for up to 10% of neoplasms of the upper urinary tract and usually manifests as hematuria. Imaging plays an important role in assessment of upper tract ...disease, unlike in bladder TCC, diagnosis of which is usually made at cystoscopy. Traditional imaging modalities, such as excretory urography, retrograde pyelography, and ultrasonography, still play pivotal roles in diagnosis of upper tract TCC, in combination with endourologic techniques. The multicentric nature of TCC makes assessment of the entire urothelium essential before treatment. The advent of minimally invasive surgery, which allows renal preservation in selected patients, makes accurate tumor staging mandatory to determine the appropriate therapy; staging is usually performed with computed tomography (CT) or magnetic resonance (MR) imaging. Vigilant urologic and radiologic follow-up is warranted to assess for metachronous lesions and recurrence. The emerging technique of CT urography allows detection of urinary tract tumors and calculi, assessment of perirenal tissues, and staging of lesions; it may offer the opportunity for one-stop evaluation in the initial assessment of hematuria and in follow-up of TCC. Similar MR imaging protocols can be used in patients who are not candidates for CT urography, although detection of urinary tract calcifications may be suboptimal.
The decay of excited states of the nucleus 135Sn, with three neutrons outside the doubly-magic 132Sn core, was studied in an experiment performed at the Radioactive Isotope Beam Factory at RIKEN. ...Several γ rays emitted from excited 135Sn ions were observed following one-neutron and one-neutron-one-proton removal from 136Sn and 137Sb beams, respectively, on a beryllium target at relativistic energies. Based on the analogy to 133Sn populated via one-neutron removal from 134Sn, an excitation energy of 695(15) keV is assigned to the 3/2− state with strongest single-particle character in 135Sn. This result provides the first direct information about the evolution of the neutron shell structure beyond N=82 and thus allows for a crucial test of shell-model calculations in this region. The experimental findings are in full agreement with calculations performed employing microscopic effective two-body interactions derived from CD-Bonn and N3LO nucleon-nucleon potentials, which do not predict a pronounced subshell gap at neutron number N=90. The occurrence of such a gap in 140Sn, i.e., when the 1f7/2 orbital is completely filled, had been proposed in the past, in analogy to the magicity of 48Ca, featuring a completely filled 0f7/2 orbital one harmonic oscillator shell below.
This study described the differences in costs and length of stay (LOS) among patients with AMI who died versus survived using a large, nationally representative cohort of AMI patients.
The 2019 HCUP ...NIS was used to analyze costs, and LOS among all patients with a principal diagnosis of AMI. A propensity-score matched analysis and multivariable regression were used to adjust for patient and hospital characteristics.
There were 4559 visits in each of the cohorts (total 9118). The adjusted mean hospital cost was $18,970 (95% CI $16,453 - $21,871) for those that survived and $23,173 (95% CI $20,167 - $26,626; p <0.001) for those that died. The LOS was 3.95 (95% CI 3.41-4.57) in survivors and 4.24 (95% CI 3.67-4.89; p <0.001) in those who died.
Survivors of AMI incurred lower costs and length of stay than those who died. Higher costs were attributed to greater LOS and higher-level care. The results suggest that economic evaluations of cardiovascular interventions that do not include the cost of dying may underestimate the benefits of the intervention.
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