Health-related quality of life in patients with generalized pustular psoriasis: A systematic literature review.

Generalized pustular psoriasis (GPP) is a rare, chronic, neutrophilic inflammatory skin disease characterized by episodes of widespread eruption of sterile, macroscopic pustules that can be accompanied by systemic inflammation and symptoms. A systematic literature review and narrative synthesis were conducted to determine the impact of GPP on patients' health-related quality of life (HRQoL) and patient-reported severity of symptoms and to compare its impact to patients with plaque psoriasis (plaque PsO). Searches were undertaken in Embase, MEDLINE and the Cochrane Library from 1 January 2002 to 15 September 2022. Screening was carried out by two reviewers independently. Outcome measures included generic (e.g. EQ-5D, SF-36) and dermatology-specific (e.g. DLQI) clinical outcome assessments, and other relevant patient-reported outcome measures (PROMs) (e.g. severity of pain measured by a numerical rating scale). Overall, 20 studies were found to be eligible for inclusion, of which seven also had data for plaque PsO. The DLQI was the most frequently reported outcome measure (16 out of 20 studies). When reported, mean DLQI (SD) scores varied from 5.7 (1.2) to 15.8 (9.6) across the studies, indicating a moderate to very large effect on HRQoL; the wide range of scores and large SDs were explained by the small population sizes (n ≤ 12 for all studies except two). Similar ranges and large SDs were also observed for other measures within individual studies. However, in general, people with GPP reported a greater impact of their skin condition on HRQoL, when compared to people with plaque PsO (i.e. higher DLQI scores) and higher severity for itch, pain and fatigue. This systematic review highlighted the need for studies with a larger population size, a better understanding of the impact of cutaneous and extracutaneous symptoms and comorbidities on HRQoL during and between GPP flares, and outcome measures specifically tailored to the unique symptoms and the natural course/history of GPP.

Receptor Tyrosine Kinases ror1/2 and ryk Are Co-expressed with Multiple Wnt Signaling Components During Early Development of Sea Urchin Embryos.

AbstractA combination of receptors, co-receptors, and secreted Wnt modulators form protein complexes at the cell surface that activate one or more of the three different Wnt signaling pathways (Wnt/ß-catenin, Wnt/JNK, and Wnt/Ca2+). Two or more of these pathways are often active in the same cellular territories, forming Wnt signaling networks; however, the molecular mechanisms necessary to integrate information from these pathways in these situations are unclear in any in vivo model system. Recent studies have implicated two Wnt binding receptor tyrosine kinases, receptor tyrosine kinase-like orphan receptor (Ror) and related-to-receptor tyrosine kinase (Ryk), in the regulation of canonical and non-canonical Wnt signaling pathways, depending on the context; however, the spatiotemporal expression of these genes in relation to Wnt signaling components has not been well characterized in most deuterostome model systems. Here we use a combination of phylogenetic and spatiotemporal gene expression analyses to characterize Ror and Ryk orthologs in sea urchin embryos. Our phylogenetic analysis indicates that both ror1/2 and ryk originated as single genes from the metazoan ancestor. Expression analyses indicate that ror1/2 and ryk are expressed in the same domains of many Wnt ligands and Frizzled receptors essential for the specification and patterning of germ layers along the early anterior-posterior axis. In addition, both genes are co-expressed with Wnt signaling components in the gut, ventral ectoderm, and anterior neuroectoderm territories later in development. Together, our results indicate that Ror and Ryk have a complex evolutionary history and that their spatiotemporal expression suggests that they could contribute to the complexity of Wnt signaling in early sea urchin embryogenesis.

Fatal invasive cerebral Absidia corymbifera infection following bone marrow transplantation.

A 56-year-old dairy farmer received a fully HLA matched unrelated donor marrow transplant for high risk CML in chronic phase. His early post-transplant course was complicated by a series of massive intracerebral bleeds and by sepsis related to a malignant otitis externa. The microbial pathogen isolated from ear swabs was found to be Absidia corymbifera, but CT scan at the time showed no intracerebral extension. Despite neutrophil engraftment and aggressive antifungal management he succumbed. Autopsy revealed invasion of Absidia into the brain from the ear. We speculate that colonisation by Absidia resulted from occupational exposure.

Synthesis, structure, and magnetic properties of Co2([N(CN)2]4bpym).H2O and M([N(CN)2]2bpym).H2O (M = Mn, Fe, Co; bpym = 2,2'-bipyrimidine).

Co2([N(CN)2]4bpym).H2O (1) and M([N(CN)2]2bpym).H2O [M = Mn (2a), Fe (2b), Co (2c); bpym = 2,2'-bipyrimidine] have been synthesized and characterized structurally and magnetically. All of the compounds crystallize in the orthorhombic space group Pnma. The unit cell parameters for 1 are a = 16.1684(5) A, b = 12.9860(3) A, c = 10.4207(3) A, and Z = 4. Compound 1 is a 2-D layered structure with water intercalated between sheets. The sheets are composed of ...M-[NCNCN]2-M-bpym-M-[NCNCN]2-M... chains, which are linked together by dicyanamides. 2a-c are isomorphic with the unit cell parameters a = 17.5112(4) A, b = 11.9955(4) A, c = 7.4684(2) A for 2a, a = 17.5814(7) A, b = 11.9453(5) A, c = 7.3292(3) A for 2b, a = 17.8642(2) A, b = 11.9216(2) A, c = 7.2860(2) A for 2c, and Z = 4 for all. They crystallize as chains containing metal centers coordinated to two bridging dicyanamides, one terminal dicyanamide, one terminal chelating bpym, and one water molecule. 2a-c are the first examples of compounds containing terminal and mu-bound dicyanamides in the same structure. The broad maximum in the magnetic susceptibility of 1 could not be fit to any known dimer models. However, the high-temperature data were fit to the Curie-Weiss expression with g = 2.86 and theta = -42 K. 2a-c could best be modeled as uniform 1-D chains with g = 2.04, theta = -0.76, and J/kB = -0.15 K for 2a, g = 2.34, theta = -7.6, and J/kB = -0.42 K for 2b, and g = 2.58, theta = -5.4, and J/kB = -1.42 K for 2c. Because of small exchange coupling throughout the extended networks, no long-range magnetic ordering was observed.

Cerebral palsy in Cape Town: A review of 389 coloured children.

Three hundred and eighty-nine Coloured cerebral palsied children were reviewed with regard to clinical type and its relationship to aetiological factors. There was no significant change in type or severity of case over two 6-year periods. Associated handicaps were also analysed, and the prevalence of these stresses the need for comprehensive assessment and treatment clinics so that multidisciplinary treatment can minimize the extent of the disabilities.

Cerebral palsy in Cape Town: a comparative 12-year retrospective study.

Three hundred and thirty-one Coloured and 175 White children with cerebral palsy, born between 1964 and 1975, were compared as regards aetiology and changing incidence over two 6-year periods. The following were the main points which emerged: (i) there is an apparent decrease in the total number of White children with cerebral palsy born in the second 6-year period, but for reasons discussed, there is probably little or no true decrease; (ii) there is a significant increase in the total number of Coloured cerebral palsied children born in the second 6-year period, due mainly to an increase in cases of cerebral palsy of perinatal origin, particularly cases of perinatal asphyxia; (iii) there is a high incidence of acquired cerebral palsy in both racial groups, but this is significantly higher amont the Coloured; (iv) ther is no racial difference in the incidence of cerebral palsy in babies of low birth weight; (v) both racial groups have a fairly high incidence of cerebral palsy due to kernicterus. It is interesting to speculate whether improved obstetric and neonatal care and the resultant lowering of perinatal mortality produce more handicapped babies.