Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III

Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families

Various neuromodulation methods including Deep Brain Stimulation of the medial forebrain bundle combined with psychopharmacotherapy of treatment-resistant depression—Case report

BackgroundTreatment-resistant depression remains one of the main concerns of modern psychiatry. Novel methods such as Transcranial Magnetic Stimulation (including deep and theta burst protocols, iTBS) and Deep Brain Stimulation (DBS) can be considered as alternative treatment options.Case presentationTwenty-nine-year-old Caucasian female, single, higher-educated was treated with major depressive disorder initially with standard pharmaco- and psychotherapy. Due to diagnosed treatment resistance additional therapeutic approaches were introduced sequentially: Electroconvulsive therapy (efficient only 4 months) and Transcranial Magnetic Stimulation (intermittent Theta Burst Stimulation, iTBS improved just insomnia). Finally the patient was enrolled to the Deep Brain Stimulation (DBS) study with the medial forebrain bundle target. After 20 months of active DBS a reduction of over 80% of depressive symptom severity was observed (Montgomery-Asberg and Hamilton Depression Rating Scales), together with an 87% reduction of anxiety symptoms intensity (Hamilton Anxiety Rating Scale) and a 90% increase in social and occupational functioning. Subjective assessment of the patient performed with questionnaires and visual analog scales showed less pronounced improvement in terms of depressive and anxiety symptoms, and high reduction of anhedonia. Some mild, transient side effects of neurostimulation were eliminated with an adjustment in stimulation parameters.ConclusionsThe presented clinical case confirms the possibility of achieving remission after the use of MFB DBS in treatment-resistant depression, but postponed for many months. Nevertheless, personalization of every combined therapy with DBS is necessary with exploration of individual factors as past traumas and personality traits. More reports on long-term observations in DBS treatment in TRD trials (especially focused on MFB target) are needed

The New Haplotypes of <i>Bartonella</i> spp. and <i>Borrelia burgdorferi</i> Sensu Lato Identified in <i>Lipoptena</i> spp. (Diptera: Hippoboscidae) Collected in the Areas of North-Eastern Poland

Deer keds are hematophagous ectoparasites (Diptera: Hippoboscidae) that mainly parasitize Cervidae. These flies are particularly important for animal health due to the occurrence of numerous pathogenic microorganisms. They may also attack humans and their bites may cause allergenic symptoms. The aim of the study was to identify the molecular characteristics of Borrelia burgdorferi sensu lato and Bartonella spp. pathogens detected in Lipoptena spp. sampled both from the hosts and from the environment. For identification of Bartonella spp and B. burgdorferi s. l., the primers specific to the rpoB and flaB gene fragments were used, respectively. The overall prevalence of B. burgdorferi s.l. DNA in Lipoptena cervi was 14.04%, including 14.8% infection in the tested group of winged specimens. The overall prevalence of Bartonella spp. was 57.02%. The presence of these bacteria was detected in 53.5% of specimens of L. cervi and 75.7% of L. fortisetosa. The phylogenetic analysis showed five new haplotypes of the rpoB gene of Bartonella sp. isolated from L. cervi/Lipoptena fortisetosa. We also identified one new haplotype of B. afzelii and three haplotypes of B. burgdorferi isolated from winged specimens of L. cervi. This is the first study to detect the genetic material of B. burgdorferi s.l. in L. cervi in Poland and the first report on the identification of these bacteria in host-seeking specimens in the environment

The First Records of Canine Babesiosis in Dogs from Dermacentor reticulatus-Free Zone in Poland

Tick-borne microorganisms belong to important etiological agents of many infectious diseases affecting humans and animals. Among them, there are haemoprotozoans of the Babesia genus, which infect erythrocytes of a host and may cause many clinical symptoms. Canine babesiosis is an emerging tick-borne disease in Southern and Central Europe. In this study, we report two cases of symptomatic canine babesiosis caused by Babesia canis in domestic dogs from the Silesian Voivodeship, Poland, as well as the presence of Dermacentor reticulatus ticks detected on one of the Babesia-infected dogs (D. reticulatus-free zone). The molecular analysis confirmed the presence of Babesia canis in the dogs blood, and the sequencing analysis showed that the obtained sequence is 100% identical to the sequence of Babesia canis isolate 3469 (sequence ID: KX712122.1). Our findings should raise awareness of B. canis infection among dog owners and veterinarians in the region where B. canis was not previously reported in residential, non-traveling dogs, as well as ensuring that adequate diagnostic methods are available.Funding Agencies|Medical University of Silesia in Katowice; [PCN-2-081/N/1/I]</p

Częstość występowania wariantu C677T genu MTHFR u pacjentów z migreną z aurą i bez aury – doniesienie wstępne

Background and purpose The aim of our study was to evaluate the frequency of the C677T variant in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with migraine with or without aura and to find an association between this variant and vascular lesions in magnetic resonance imaging of the head, presence of patent foramen ovale (PFO) and increased level of homocysteine. Material and methods Ninety-one patients with migraine, aged 19–57, were investigated in this study. The MTHFR C677T variant was genotyped in this group and levels of homocysteine, folic acid and vitamin were measured. Transcranial Doppler sonography with test for PFO detection by injection of air contrast during the Valsalva manoeuvre was performed in each patient. Results Frequency of the C677T variant in the MTHFR gene was similar in patients and controls. Hyperhomocysteinaemia was significantly more frequent in migraine patients with the C677T variant. The prevalence of PFO was significantly higher in migraine patients with aura and the homozygous variant of the MTHFR gene. Conclusions Frequency of the C677T variant in the MTHFR gene was similar in patients and controls. Significantly more frequent prevalence of PFO in migraine patients with aura (with homozygous recessive genotype of MTHFR) probably suggests their common genetic basis. Hyperhomocysteinaemia was significantly more frequent in migraine patients with the C677T variant, which could be an additional risk factor of this disease.Wstęp i cel pracy Celem pracy była ocena częstości występowania wariantu C677T genu MTHFR u chorych na migrenę oraz określenie, czy istnieje związek pomiędzy wariantem genu a stężeniem homocysteiny w surowicy, obecnością ogniskowych zmian naczyniopochodnych w badaniu za pomocą rezonansu magnetycznego (RM) głowy oraz występowaniem drożnego otworu owalnego. Materiał i metody Badaniem objęto 91 chorych. U wszystkich wykonano rutynowe badanie neurologiczne i internistyczne, oznaczenia stężenia witaminy B12, kwasu foliowego i homocysteiny w surowicy, badanie na obecność wariantu C677T genu MTHFR, badanie dopplerowskie tętnic mózgowych z podaniem kontrastu celem diagnostyki drożnego otworu owalnego, a także RM głowy. Wyniki Częstość występowania wariantu C677T genu MTHFR była podobna u osób z migreną i w grupie kontrolnej. Zwiększone stężenie homocysteiny w surowicy obserwowano znamiennie częściej u chorych na migrenę, u których stwierdzono obecność wariantu C677T genu MTHFR. Drożny otwór owalny występował znamiennie częściej u chorych na migrenę z aurą, u których stwierdzono obecność homozygoty wariantu C677T genu MTHFR. Wnioski Częstość występowania wariantu C677T genu MTHFR u pacjentów z migreną jest podobna jak u osób bez tej choroby. Znamiennie częstsze występowanie drożnego otworu owalnego u osób z migreną z aurą, u których stwierdzono obecność homozygoty wariantu C677T genu MTHFR, mogłoby sugerować związek tego typu migreny z anomalią rozwojową serca i ich ewentualne wspólne podłoże genetyczne. Znamiennie częstsze występowanie zwiększonego stężenia homocysteiny w surowicy u pacjentów z migreną, u których stwierdzono obecność wariantu C677T genu MTHFR mogłoby być dodatkowym czynnikiem ryzyka wystąpienia migreny

Mental Health of Medical and Non-Medical Professionals during the Peak of the COVID-19 Pandemic: A Cross-Sectional Nationwide Study

Background: The study aimed to compare psychopathological expressions during the COVID-19 (novel coronavirus disease 2019) pandemic, as declared on March 11th 2020 by the World Health Organization, with respect to which institutional variables might distinguish the impact of COVID-19 in medical and non-medical professionals. Methods: A cross-sectional study was performed nationwide between 16th March and the 26th April 2020 in Poland. A total of 2039 respondents representing all healthcare providers (59.8%) as well as other professionals filled in the sociodemographic section, the General Health Questionnaire-28 and the author&rsquo;s questionnaire with questions related to exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the availability of protective measures, quarantine, change of working hours and place of employment during the pandemic, as well as feelings associated with the state of the pandemic. Results: Medical professionals more often presented with relevant psychopathological symptoms (GHQ-28 (General Health Questionnaire-28) total score &gt;24) than the non-medical group (60.8% vs. 48.0%, respectively) such as anxiety, insomnia and somatic symptoms even after adjustment for potential confounding factors. Male sex, older age and appropriate protective equipment were associated with significantly lower GHQ-28 total scores in medical professionals, whereas among non-medical professionals, male sex was associated with significantly lower GHQ-28 total scores. Conclusions: Somatic and anxiety symptoms as well as insomnia are more prevalent among medical staff than workers in other professions. Targeting the determinants of these differences should be included in interventions aimed at restoring psychological well-being in this specific population. Apparently, there are present gender differences in psychological responses that are independent of profession

Mutations in COL1A1 and COL1A2 Genes Associated with Osteogenesis Imperfecta (OI) Types I or III.

Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families

Telomere Length in Elderly Caucasians Weakly Correlates with Blood Cell Counts

Background. Age-related decrease in bone marrow erythropoietic capacity is often accompanied by the telomere length shortening in peripheral white blood cells. However, limited and conflicting data hamper the conclusive opinion regarding this relationship. Therefore, the aim of this study was to assess an association between telomere length and peripheral blood cell count parameters in the Polish elderly population. Material and Methods. The substudy included 1573 of 4981 subjects aged 65 years or over, participants of the population-based PolSenior study. High-molecular-weight DNA was isolated from blood mononuclear cells. Telomere length (TL) was measured by QRT-PCR as abundance of telomere template versus a single gene copy encoding acidic ribosomal phosphoprotein P0. Results. Only white blood count (WBC) was significantly different in TL tertile subgroups in all subjects (P=0.02) and in men (P=0.01), but not in women. Merely in men significant but weak positive correlations were found between TL and WBC (r=0.11, P<0.05) and RBC (r=0.08, P<0.05). The multiple regression analysis models confirmed a weak, independent contribution of TL to both RBC and WBC. Conclusions. In the elderly, telomere shortening limits hematopoiesis capacity to a very limited extent