Rak dojke najčešća je novotvorina i peti uzrok smrti žena. Etiologija i patogeneza ovoga zloćudnog tumora su multifaktorske. Pojava neoplazma u primatelja solidnih organa liječenih imunosupresivnim ...lijekovima je 2 do 3 puta veća nego u općoj populaciji. U rizičnoj populaciji su i žene s presađenim bubregom. Cilj ovoga pregleda literature je istražiti povezanost pojavnosti karcinoma dojke u primatelja bubrežnog presatka i imunosupresivnih režima, opisati njihovu ulogu u tom procesu te istražiti trenutne preporuke probira za rano otkrivanje karcinoma dojke u toj populaciji. Kako bismo pristupili potrebnoj literaturi koristili smo bazu podataka PubMed-a. MeSH pojmovi uporabljeni za pretragu baze literature su bili: “breast cancer”; “risk factors”; “cancer screening”; “kidney transplantation”; “immunosuppression” i “cancer”. Nakon primjene kriterija isključenja ukupno je pregledano 409 članaka. Članci su uključivali randomizirana kontrolna istraživanja, preglede i sustavne preglede literature. Uporabljene su i reference s drugih pregleda literature kako bi se pribavile dodatne relevantne informacije koje potencijalno nisu bile dohvaćene pri inicijalnoj pretrazi. Karcinom dojke najdijagnosticiraniji je karcinom i ujedno peti vodeći uzrok smrti žena u svijetu. Karcinom dojke je na trećem mjestu liste malignih uzročnika smrti, odmah iza karcinoma pluća i kolorektalnog karcinoma. Karcinom dojke je uzrokovan kombinacijom hormonskih i genetskih
čimbenika te čimbenika vezanih uz starenje. Značajan čimbenik procesa kancerogeneze je imunosupresija, što potvrđuje dva do tri puta češća pojavnost malignih bolesti u populaciji primatelja transplantiranih organa. Kronična imunosupresivna terapija, okolišni čimbenici (izlaganje sunčevu zračenju) i genetički zapisi pojedinaca utječu na proces razvoja malignih bolesti u primatelja transplantiranih organa. Imunosupresivni lijekovi smanjuju imuni nadzor, što pospješuje proces virusne onkogeneze te opće karcinogeneze. Primatelji bubrežnog presatka skloniji su razvoju karcinoma upravo zbog doživotne imunosupresivne terapije pa je karcinom drugi uzročnik smrtnosti kod te populacije. Od iznimne važnosti je spomenuti da razlike u procijenjenom riziku razvoja karcinoma ovise upravo o vrsti karcinoma. Pokazalo se da imunosupresija ne utječe na određene maligne bolesti poput karcinoma dojke, jer je njihov relativni rizik usporediv s onim u općoj populaciji. Zbog ograničenog broja radova koji se bave tematikom karcinoma dojke nakon transplantacije bubrega ovom prigodom predstavljamo sveobuhvatan pregled dosadašnje literature, trenutnog razumijevanja patofi ziologije bolesti, uloge probira u- njenoj dijagnozi i liječenju. Opsežnim pregledom literature došli smo do zaključka da rizik razvoja karcinoma dojke nakon transplantacije u primatelja bubrežnog presatka nije povećan u usporedbi s općom populacijom. Iz pregledanih radova proizlazi zaključak da razvoj karcinoma dojke u primatelja bubrežnog presatka nije povezan s post-transplantacijskim imunosupresivnim režimom te je uglavnom povezan sa starenjem i neovisnim čimbenicima rizika koji sami po sebi mogu dovesti do transplantacije bubrega, kao što je dijabetes melitus. Zbog programa probira za rano otkrivanje karcinoma post-transplantacijski karcinom dojke obično se dijagnosticira rano. Međutim, ako ga se dijagnosticira u uznapredovalim
stadijima povezan je sa značajno lošijim ishodom i povećanom razinom smrtnosti u usporedbi s općom populacijom. Preporuka je da se probir bolesnika provodi zajedno s općom populacijom koja odgovara dobi i spolu bolesnika s presatkom, uz naglasak na individualni pristup svakom bolesniku. Iznimno je važno napomenuti da je ovo područje medicine koje zahtijeva daljnje istraživanje. Zbog rijetkosti post-transplantacijskog karcinoma dojke i oskudnih resursa na tu tematiku većina smjernica ekstrapolirana je iz opće populacije i ne odgovara minimalnom riziku od razvoja te bolesti. Slično tome, smjernice za liječenje izvedene su iz podataka opće populacije i ne uzimaju u obzir posebna razmatranja kod populacije pacijenata s bubrežnim presatkom kao: održavanje funkcionalnog presatka, odbacivanje presatka, nefrotoksične kemoterapijske lijekove i istodobnu primjenu imunosupresivnih lijekova. Potrebno je spomenuti da je heterogenost rezultata o kojima se raspravlja u našem pregledu literature posljedica različitih vrsta imunosupresivnih režima, transplantiranih organa, pridruženih bolesti, duljine praćenja bolesnika i programa probira. Kako bi se defi nirale jasne smjernice prilagođene ovoj populaciji, potrebno je daljnje istraživanje mehanizama nastanka bolesti, uz produljeno vrijeme praćenja pacijenata na različitim imunosupresivnim režimima kako bi se omogućila naknadna usporedba.
Abstract
Background
Outpatient coronavirus disease 2019 (COVID-19) has been insufficiently characterized. To determine the progression of disease and determinants of hospitalization, we conducted a ...prospective cohort study.
Methods
Outpatient adults with positive reverse transcription polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited by phone between April 21 and July 23, 2020, after receiving outpatient or emergency department testing within a large health network in Maryland, United States. Symptoms were collected by participants on days 0, 3, 7, 14, 21, and 28, and portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected for 15 consecutive days. Baseline demographics, comorbid conditions, and vital signs were evaluated for risk of subsequent hospitalization using negative binomial and logistic regression.
Results
Among 118 SARS-CoV-2-infected outpatients, the median age (interquartile range IQR) was 56.0 (50.0–63.0) years, and 50 (42.4%) were male. Among individuals in the first week of illness (n = 61), the most common symptoms included weakness/fatigue (65.7%), cough (58.8%), headache (45.6%), chills (38.2%), and anosmia (27.9%). Participants returned to their usual health a median (IQR) of 20 (13–38) days from symptom onset, and 66.0% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. The area under the receiver operating characteristics curve for the initial home SaO2 for predicting subsequent hospitalization was 0.86 (95% CI, 0.73–0.99).
Conclusions
Symptoms often persisted but uncommonly progressed to hospitalization among outpatients with COVID-19. Home SaO2 may be a helpful tool to stratify risk of hospitalization.
Potassium channels play a critical role in defining the electrophysiological properties accounting for the unique response patterns of auditory neurons. Serial analysis of gene expression (SAGE), ...microarrays, RT-PCR, and real-time RT-PCR were used to generate a broad profile of potassium channel expression in the rat cochlear nucleus. This study identified mRNAs for 51 different potassium channel subunits or channel interacting proteins. The relative expression levels of 27 of these transcripts among the AVCN, PVCN, and DCN were determined by real-time RT-PCR. Four potassium channel transcripts showed substantial levels of differential expression. Kcnc2 was expressed more than 15-fold higher in the DCN as compared to AVCN and PVCN. In contrast, Kcnj13 had an approximate 10-fold higher expression in AVCN and PVCN than in DCN. Two subunits that modify the activity of other channels were inversely expressed between ventral and dorsal divisions. Kcns1 was over 15-fold higher in DCN than AVCN or PVCN, while Kcns3 was about 25-fold higher in AVCN than in DCN. The expression patterns of potassium channels in the subdivisions of the cochlear nucleus provide a basis for understanding the electrophysiological mechanisms which sub-serve central auditory processing and provide targets for further investigations into neural plastic changes that occur with hearing loss.
Cochlear nucleus neurons propagate auditory impulses to higher brain stem centers at rapid firing rates with high fidelity. Intrinsic to synaptic transmission are the SNARE (soluble
...N-ethylmaleimide-sensitive factor attachment protein receptor) proteins engaged in vesicle fusion, release and recycling. Herein we report a novel splice variant of the SNARE protein Vamp1 (vesicle-associated membrane protein 1) within the cochlear nucleus. We previously demonstrated, through serial analysis of gene expression and microarray studies, that Vamp1 is differentially expressed among the subdivisions of the rat cochlear nucleus. The 3′ end of this transcript, however, was poorly characterized and we could not initially confirm our findings. In this study, we designed RT-PCR primers using conserved 5′ regions and the mouse 3′ domain to validate the expression of Vamp1. Several species of Vamp1 were subsequently amplified from a rat brain cDNA library including a full length clone of Vamp1as and a novel splice variant we termed Vamp1nv. Using regional brain libraries Vamp1nv showed expression in the medulla and lack of expression in the cortex, cerebellum and thalamus. Expression of Vamp1nv was further confirmed and characterized by RT-PCR and real-time PCR in each of the cochlear nucleus subdivisions. The predicted protein sequence for Vamp1nv demonstrates a unique modification of the carboxy-terminal end of the protein as compared to known variants. This includes the appearance of two intra-vesicular serine residues with high predicted potential as kinase phosphorylation sites. Such splice variants of Vamp1 may alter the kinetics of SNARE complex formation and vesicle release and impart unique features to expressing neurons. This may be important for central auditory function and contribute to the distinct physiological properties observed in auditory neurons.
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