Pengembangan Modul Intervensi Untuk Meningkatkan Resiliensi Pada Individu Yang Mengalami Perubahan Fisik Menjadi Penyandang Disabilitas

Penelitian ini bertujuan untuk menindaklanjuti temuan sebelumnya dengan mengembangkan modul intervensi secara terperinci, yang selanjutnya dapat digunakan sebagai panduan dalam membantu meningkatkan resiliensi individu yang mengalami Perubahan kondisi fisik menjadi penyandang disabilitas. Penulis menyusun serta merinci rancangan implementasi awal yang direkomendasikan oleh penelitian sebelumnya kedalam langkah-langkah yang lebih sistematis dan operasional hingga memperoleh hasil akhir berupa modul. Metode yang digunakan berbasis tahapan riset aksi, meskipun proses yang dilakukan hanya sampai pada langkah ketiga, yaitu Perumusan solusi dari persoalan yang diangkat. Partisipan terdiri dari delapan individu yang mengalami Perubahan kondisi menjadi penyandang disabilitas. Selain partisipan, empat orang psikolog juga dilibatkan dalam penelitian ini sebagai penelaah modul. Hasil penelitian ini berupa sebuah paket modul intervensi untuk peningkatan resiliensi melalui penguatan faktor protektif serta pengembangan strategi koping dan adaptasi pada individu yang mengalami Perubahan kondisi fisik menjadi penyandang disabilitas. Paket modul tersebut terdiri dari 5 sub-modul yang telah disusun sedemikian rupa untuk memudahkan pelaksanaannya, terdiri dari modul: (1) memperkuat dukungan keluarga terhadap penyandang disabilitas; (2) pendampingan awal penyandang disabilitas; (3) intervensi lanjut 1 (penguatan faktor protektif internal); (4) intervensi lanjut 2 (pengembangan strategi koping); dan (5) intervensi lanjut 3 (langkah adaptasi positif)

NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease

The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase–associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-0.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167μg uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164μg uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

Background The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. Methods We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. Results We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10(-14)). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. Conclusions We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.)

Both “illness and temptation of the enemy”: melancholy, the medieval patient and the writings of King Duarte of Portugal (r. 1433–38)

Recent historians have rehabilitated King Duarte of Portugal, previously maligned and neglected, as an astute ruler and philosopher. There is still a tendency, however, to view Duarte as a depressive or a hypochondriac, due to his own description of his melancholy in his advice book, the Loyal Counselor. This paper reassesses Duarte's writings, drawing on key approaches in the history of medicine, such as narrative medicine and the history of the patient. It is important to take Duarte's views on his condition seriously, placing them in the medical and theological contexts of his time and avoiding modern retrospective diagnosis. Duarte's writings can be used to explore the impact of plague, doubt and death on the life of a well-educated and conscientious late-medieval ruler

Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia

PURPOSE OF REVIEW: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin superfamily of carrier proteins. NGAL is the first known mammalian protein which specifically binds organic molecules called siderophores, which are high-affinity iron chelators. Here, we review the expression, siderophore-dependent biological activities and clinical significance of NGAL in epithelial development and in kidney disease. RECENT FINDINGS: NGAL expression is rapidly induced in the nephron in response to renal epithelial injury. This has led to the establishment of NGAL assays that detect renal damage in the human. Additionally, only when complexed with siderophore and iron as a trimer, NGAL induces mesenchymal-epithelial transition (or nephron formation) in embryonic kidney in vitro and protects adult kidney from ischemia-reperfusion injury in vivo. While the structure of the NGAL: siderophore: iron complex has thus far only been solved for bacterially synthesized siderophores, new evidence suggests the presence of mammalian siderophore-like molecules. SUMMARY: NGAL is rapidly and massively induced in renal epithelial injury and NGAL: siderophore: iron complexes may comprise a physiological renoprotective mechanism. The data have implications for the diagnosis and treatment of acute renal injury

MSANTD3 immunostaining of salivary gland benign and malignant specimens.

<p>MSANTD3 immunostaining of salivary gland benign and malignant specimens.</p

MSANTD3 structural domains and phylogenetic conservation.

<p><b>(A)</b> Schematic depiction of MSANTD3 domains, showing the location of the Myb/SANT-like domain within the N-terminus. <b>(B)</b> Schematic depiction of MSANTD3 MACAW sequence alignments across species. Boxes indicate conserved blocks, while the shading indicates pair-wise scores relative to human MSANTD3 with colors indicated in the key. <i>Above</i>, the horizontal black bar indicates the location of the conserved Myb/MSANT domain found by NCBI search (Pfam 13873). <b>(C)</b> Actual MACAW alignment within the MYB/SANT region. <b>(D)</b> Phylogenetic tree based on the global alignment made by ClustalX and visualized using Treeview software.</p

MSANTD3 immunostaining across diverse benign and neoplastic tissues.

<p>MSANTD3 immunostaining across diverse benign and neoplastic tissues.</p

Novel genes fusions in acinic cell carcinoma.

<p><b>(A)</b> Predicted structure of the <i>HTN3</i>-<i>MSANTD3</i> fusion gene. Exon 1 (non-coding) of <i>HTN3</i> is fused to the exon 2 (first coding exon) of <i>MSANTD3</i>, leading to predicted overexpression of full-length MSANTD3 protein (translation start site is indicated). Fusion junction-spanning sequence reads are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0171265#pone.0171265.s001" target="_blank">S1 Fig</a>. <b>(B)</b> Predicted structure of the <i>PRB3</i>-<i>ZNF217</i> gene fusion. Here, exon 2 (coding) of <i>PRB3</i> is fused to exon 2 (first coding) of <i>ZNF217</i>, possibly leading to the overexpression (by internal initiation of translation) of full-length ZNF217 protein. Fusion junction-spanning sequence reads are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0171265#pone.0171265.s002" target="_blank">S2 Fig</a>.</p