Systematic description of COVID-19 pandemic using exact SIR solutions and Gumbel distributions.

An epidemiological study is carried out in several countries analyzing the first wave of the COVID-19 pandemic using the SIR model and Gumbel distribution. The equations of the SIR model are solved exactly using the proper time as a parameter. The physical time is obtained by integration of the inverse of the infected function over proper time. Some properties of the solutions of the SIR model are studied such as time scaling and the asymmetry, which allows to obtain the basic reproduction number from the data. Approximations to the solutions of the SIR model are studied using Gumbel distributions by least squares fit or by adjusting the maximum of the infected function. Finally, the parameters of the SIR model and the Gumbel function are extracted from the death data and compared for the different countries. It is found that ten of the selected countries are very well described by the solutions of the SIR model, with a basic reproduction number between 3 and 8.

The ultrastructure of muscle fibers and satellite cells in experimental autoimmune encephalomyelitis after treatment with transcranial magnetic stimulation.

In this study, we investigated the effect of transcranial magnetic stimulation (TMS) on the ultrastructure of muscle fibers and satellite cells in rats with experimental autoimmune encephalomyelitis (EAE). EAE-induced animals were treated with TMS (60 Hz at 0.7 mT) for 2 hours in the morning, once a day, 5 days a week, for 3 weeks, starting on day 15 post-immunization. The rats were sacrificed on day 36 post-immunization, and the soleus muscles were evaluated by light microscopy and transmission electron microscopy. Findings were compared with a non-treated EAE group. Electron microscopy analysis showed the presence of degenerated mitochondria, autophagic vacuoles, and altered myofibrils in non-treated EAE group. This correlates with the presence of acid phosphatase activity in muscle fibers and core-targetoid lesions with desmin immunohistochemistry. Most myonuclei in the EAE group showed apoptotic features. In contrast, EAE induced-TMS treated animals had less ultrastructural changes in the mitochondria and the myofibrils, together with less frequent apoptotic nuclear features. Peripheral desmin+ protrusions, as a marker of active satellite cells, were significantly increased in TMS-treated group. This correlates ultrastructurally with the presence of active features in satellite cells in the TMS group. In conclusion, the attenuation of ultrastructural alterations in muscle fibers and activation response of satellite cells caused by EAE indicated that skeletal muscle had a regenerative response to TMS.

Meson-exchange currents and quasielastic antineutrino cross sections in the superscaling approximation.

We evaluate quasielastic double-differential antineutrino cross sections obtained in a phenomenological model based on the superscaling behavior of electron scattering data and estimate the contribution of the vector meson-exchange currents in the two-particle-two-hole sector. We show that the impact of meson-exchange currents for charge-changing antineutrino reactions is much larger than in the neutrino case.

Impact of BK Polyomavirus Plasma Viral Load in Kidney Transplant Outcomes.

BACKGROUND: BK polyomavirus infection (BKVi) is an important cause of kidney transplant (KT) loss, but there is scarce evidence on the impact of BK plasma viral load on graft function and long-term KT survival. METHODS: A retrospective cohort study including all KT recipients with BKVi (BK viremia identified in ≥3 consecutive samples by polymerase chain reaction) in our center from January 2010 to December 2020 was performed. A case-control study (1:2) was performed. We grouped the cases according to their highest peak viral load: low-level viremia (<10,000 copies/mL) and high-level viremia (≥10,000 copies/mL). To identify risk factors for BKVi, a logistic regression analysis was achieved, and a multivariable Cox regression was used to describe risk factors for graft loss. RESULTS: A total of 849 KTs were performed, and 67 presented BKVi (low-level viremia, n = 35 and high-level viremia, n = 26). In logistic regression analysis male sex (odds ratio [OR], 4.226; 95% CI, 1.660-10.758, P = .002), age (OR, 1.047; 95% CI, 1.008-1.088; P = .018), and retransplant (OR, 4.162; 95% CI, 1.018-17.015; P = .047) were predictors of BKVi. Acute rejection was more frequent in the BKVi group (18% vs 4.9%, P = .004), and graft survival was lower in patients with BKVi and high-level viremia (P = .027). In Cox regression analysis, BKVi (hazard ratio, 3.657; 95% CI, 1.146-11.670; P = .029) and specific BKV (BK polyomavirus) high-level viremia (hazard ratio, 1.988; 95% CI, 1.012-3.907; P = .046) were predictors of shorter graft survival. CONCLUSIONS: BKV high-level viremia was associated with BKV nephropathy and poorer graft survival. Additionally, acute rejection is more frequent after BKVi. It is necessary to develop strategies safe and effective for these patients.

Biological effects of sodium fluoride varnishes used in remineralisation of enamel: An in vitro study.

AIM: During the last three decades, fluoride varnishes have been recognised as effective strategies for caries prevention in the young-child population and have contributed to a decrease in its prevalence worldwide. The present study aimed to assess in vitro the level of cytotoxicity and genotoxicity in human primary pulp fibroblasts (DPFs) of two NaF varnishes. MATERIALS AND METHODS: Four experimental assays were carried out (MTS, Mitotracker® system [mitochondrial function and morphology], Live/Dead®, and Comet) to assess the morphology, viability, and genotoxicity of two NaF varnishes (Duraphat® and Clinpro White®, both at two different concentrations). The essays were conducted on cultured pulp fibroblasts, grouped in four experimental and two control groups. Collected data were analysed by one-way ANOVA followed by the post hoc Bonferroni test. RESULTS: Some morphological changes of DPFs could be detected after the NaFVs stimulation. Most DPFs incubated in Duraphat (22.6 mg/L) maintained their morphological characteristics, except for a small decrease in cell size and shorter cytoplasmic projections (filopodia); DPFs treated with Clinpro White Varnish (22.6 mg/L) presented a morphology and size similar to the control group. DPFs exposed to Duraphat (113 mg/L) exhibited significant morphological alterations with considerable cell size increases and DPFs treated with Clinpro White Varnish (113 mg/L) showed a slight cell size increase without noticeable morphological anomalies. The Duraphat (22.6 mg/L) and Clinpro White Varnish (22.6 mg/L) groups promoted 31% and 35% cell proliferation, respectively, whereas DPFs proliferation with Duraphat (113 mg/L) decreased up to 59%, and cell proliferation with Clinpro White Varnish (113 mg/L) was similar to that of control. CONCLUSION: All tested varnishes induced changes in the fibroblastic mitochondria. In general, Duraphat was less biocompatible and caused a change in the number of mitochondria compared to Clinpro White Varnish.

Culture and the anxiety disorders: recommendations for DSM-V.

BACKGROUND: The anxiety disorders specified in the fourth edition, text revision, of The Diagnostic and Statistical Manual (DSM-IV-TR) are identified universally in human societies, and also show substantial cultural particularities in prevalence and symptomatology. Possible explanations for the observed epidemiological variability include lack of measurement equivalence, true differences in prevalence, and limited validity or precision of diagnostic criteria. One central question is whether, through inadvertent "over-specification" of disorders, the post-DSM-III nosology has missed related but somewhat different presentations of the same disorder because they do not exactly fit specified criteria sets. This review canvases the mental health literature for evidence of cross-cultural limitations in DSM-IV-TR anxiety disorder criteria. METHODS: Searches were conducted of the mental health literature, particularly since 1994, regarding cultural or race/ethnicity-related factors that might limit the universal applicability of the diagnostic criteria for six anxiety disorders. RESULTS: Possible mismatches between the DSM criteria and the local phenomenology of the disorder in specific cultural contexts were found for three anxiety disorders in particular. These involve the unexpectedness and 10-minute crescendo criteria in Panic Disorder; the definition of social anxiety and social reference group in Social Anxiety Disorder; and the priority given to psychological symptoms of worry in Generalized Anxiety Disorder. Limited evidence was found throughout, particularly in terms of neurobiological markers, genetic risk factors, treatment response, and other DSM-V validators that could help clarify the cross-cultural applicability of criteria. CONCLUSIONS: On the basis of the available data, options and preliminary recommendations for DSM-V are put forth that should be further evaluated and tested.

Increased Functional Connectivity After Listening to Favored Music in Adults With Alzheimer Dementia.

BACKGROUND: Personalized music programs have been proposed as an adjunct therapy for patients with Alzheimer disease related dementia, and multicenter trials have now demonstrated improvements in agitation, anxiety, and behavioral symptoms. Underlying neurophysiological mechanisms for these effects remain unclear. METHODS: We examined 17 individuals with a clinical diagnosis of Alzheimer disease related dementia using functional MRI following a training period in a personalized music listening program. RESULTS: We find that participants listening to preferred music show specific activation of the supplementary motor area, a region that has been associated with memory for familiar music that is typically spared in early Alzheimer disease. We also find widespread increases in functional connectivity in corticocortical and corticocerebellar networks following presentation of preferred musical stimuli, suggesting a transient effect on brain function. CONCLUSIONS: Findings support a mechanism whereby attentional network activation in the brain's salience network may lead to improvements in brain network synchronization.

Clinical and molecular findings in a cohort of ANO5-related myopathy.

OBJECTIVE: ANO5-related myopathy is an important cause of limb-girdle muscular dystrophy (LGMD) and hyperCKemia. The main descriptions have emerged from European cohorts, and the burden of the disease worldwide is unclear. We provide a detailed characterization of a large Brazilian cohort of ANO5 patients. METHODS: A national cross-sectional study was conducted to describe clinical, histopathological, radiological, and molecular features of patients carrying recessive variants in ANO5. Correlation of clinical and genetic characteristics with different phenotypes was studied. RESULTS: Thirty-seven patients from 34 nonrelated families with recessive mutations of ANO5 were identified. The most common phenotype was LGMD, observed in 25 (67.5%) patients, followed by pseudometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCKemia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patients presented axial involvement, including one patient with isolated axial weakness. The most affected muscles according to MRI were the semimembranosus and gastrocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants in ANO5 were identified, and the c.191dupA was present in 19 (56%) families. Sex, years of disease, and the presence of loss-of-function variants were not associated with specific phenotypes. INTERPRETATION: We present the largest series of anoctaminopathy outside Europe. The most common European founder mutation c.191dupA was very frequent in our population. Gender, disease duration, and genotype did not determine the phenotype.

New granulocyte antigens demonstrated by microgranulocytotoxicity assay.

Although granulocyte transfusions and bone marrow transplantation are becoming common clinical modalities, our knowledge of surface nonerythroid, nonlymphoid, non-HLA hematopoetic antigens remains very incomplete. Accordingly, we have systematically screened sera from recipients of multiple granulocyte and whole blood transfusions, and immunoneutropenic patients for antibodies directed primarily at granulocytes. The initial screens demonstrated that >50% of the sera from the above sources contained non-HLA cytotoxic and/or agglutinating antibodies. Preliminary clustering indicated seven possible new specificities detected by microgranulocytotoxicity. Calculations for Hardy-Weinberg goodness of fit based on a study of 98 unrelated donors plus informative families established that 5 of these were alleles of a single new locus termed Human Granulocyte Antigen (HGA)-3a, b, c, d, and e. Absorptions indicated that these antigens were present on mature granulocytes but absent from platelets, lymphocytes, monocytes, and myeloid precursors. A single antigen of another separate locus, HGA-1, was also identified. Absorptions revealed a quite different distribution for HGA-1 than HGA-3, this antigen being detected on monocytes and myeloblasts as well as on mature granulocytes. Independent segregation of the three loci from HLA, from the NA-NB and the 5a-5b antigens, and from themselves was confirmed in informative families.Finally, it seems likely that other antigens will be identified because several other sera that react with both monocytes and granulocytes have been detected.

Interventions for treating posterior cruciate ligament injuries of the knee in adults.

BACKGROUND: Injuries of the posterior cruciate ligament (PCL) of the knee frequently occur in automobile accidents and sports injuries, although they are less frequent overall than injuries of the anterior cruciate ligament (ACL). Some patients show significant symptoms and subsequent articular deterioration, while others are essentially asymptomatic, maintaining habitual function. Management of PCL injuries remains controversial and prognosis can vary widely. Interventions extend from non-operative (conservative) procedures to reconstruction of the PCL, in the hope that the surgical procedure may have a positive effect in the reduction/prevention of future osteoarthritic changes in the knee. OBJECTIVES: To determine the effectiveness and safety of surgical and conservative interventions for PCL injuries in adults. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group Specialised Register (April 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE via PubMed (1966 to April 2004), EMBASE (1966 to April 2004), CINAHL (1982 to April 2004), LILACS (1982 to April 2004), SportsDiscus (1975 to April 2004), and reference lists of articles. SELECTION CRITERIA: Randomized or quasi-randomized clinical trials comparing various methods of operative and conservative interventions, and comparisons with each other for the treatment of PCL injuries. DATA COLLECTION AND ANALYSIS: References found with the search strategy were evaluated independently by two review authors. MAIN RESULTS: No randomized or quasi-randomized controlled studies meeting the selection criteria were identified. AUTHORS' CONCLUSIONS: Future research should include randomized controlled trials of acute isolated PCL injuries, or PCL injuries when combined with other ligament injuries of the knee, treated operatively and conservatively. Adequate numbers of patients and an objective methodology for patient evaluation must be used in future studies of these interventions to determine the long-term results.

Reduction and repopulation of T-lymphocytes after cytoreductive therapy with or without autologous bone marrow rescue.

The reconstitution of peripheral-blood T-lymphocytes following cytoreductive therapy in standard (11 patients) or in high dosages (ten patients) was compared with that after supralethal cytoreductive therapy followed by autologous bone marrow rescue (ABMR, 20 patients). Along with the increasing cytotoxic potential of the three therapy protocols, T-cell counts fell to lower levels. Following all three forms of cytoreductive therapy, T8+ T-cell counts decreased to lower levels than T4+ T-cell counts. The greater relative reduction of T8+ T cells may indicate that T8+ T cells are more sensitive to cytoreductive therapy than T4+ T cells, and/or that T8+ T cells have shorter survival times. The contribution of residual (mainly T4+) T cells to the T-cell repopulation was significant in the patients on standard-dosage chemotherapy, less important in those on high-dosage chemotherapy, and minor in those receiving supralethal cytoreductive therapy and ABMR. The repopulation rates of T8+ T cells following ABMR exceeded those observed after chemotherapy without ABMR. The T3- (T3 negative) T-cell subset, which comprises only 5%-10% of peripheral T cells in normal individuals, decreased rapidly to low levels and remained so for the entire six-week observation period in both chemotherapy groups. Following ABMR, however, those T3- T cells rapidly increased again to normal levels. Since the T cells in bone marrow biopsies have a large T3- fraction, that rapid recovery of T3- T cells may reflect the contribution of marrow precursors in the marrow grafts to the improved T-cell regeneration following ABMR.

Reduction and repopulation of recipient T4+ and T8+ T-lymphocytes in allogeneic bone marrow transplantation.

In eight recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repopulation of T4+ and T8+ T-lymphocytes of recipient origin were studied. The origin of the donor-recipient T4+ and T8+ T cells was studied using quinacrine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of five (range 1-8) days after BMT. T8+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells that appeared in the circulation at day 12 were predominantly T4+, and a large number of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection.

Effect of cytomegalovirus infection on T-lymphocytes after lymphocyte-depleted bone marrow transplantation.

The effect of cytomegalovirus (CMV) infection on the repopulation of the peripheral blood with T-lymphocytes was studied in recipients of lymphocyte-depleted bone marrow transplants (BMT) who had hematologic and cytogenetic evidence of engraftment. Lymphocyte depletion was performed using counterflow centrifugation and resulted in a median depletion of 98.4% (range 94.4%-99.8%) of the T cells. Between 8 and 105 days after BMT, the T-cell repopulation was characterized by a relative preponderance of T cells lacking the CD3 marker and a slow repopulation of CD3+, CD4+, and CD8+ T cells. The CD8+ T cells repopulated at a faster rate in patients with CMV infection than in those not infected with CMV. At the end of the 9- to 12-month follow-up period, patients with CMV infection had normal numbers of CD4+ and CD8+ T cells but increased numbers of HNK1+ T cells. Those without CMV infection had subnormal numbers of CD4+ T cells, normal numbers of CD8+ T cells, and numbers of HNK1+ T cells that attained the upper limit of the normal range. Most of the HNK1+ T cells in both patient groups coexpressed the CD8 marker. We conclude that the occurrence of CMV infection in recipients of lymphocyte-depleted BMT is associated with an increase in the number of T cells coexpressing CD8 and HNK1, just as in recipients of nondepleted BMT.

Marrow donor immunity to herpes simplex virus: association with acute graft-versus-host disease.

The interactions between humoral and cellular immunity to herpes simplex virus (HSV) in bone marrow donors, the occurrence of active HSV infections, and the development of grades II-IV acute graft-versus-host disease (GVHD) in their HLA-A,B,C,DR-identical sibling recipients were studied. The absence of IgG-class HSV antibodies in the marrow donors was associated with a low incidence of GVHD: 38 of 53 recipients (72%) of marrow from HSV-seropositive donors developed GVHD versus only two of 15 recipients (13%) with HSV-seronegative donors (p = 0.0004). The cellular immunity to HSV was studied in vitro by evaluating the degree of lymphocyte proliferative responses to that virus and was also significantly associated with GVHD: 30 of 43 recipients (70%) of marrow from donors with a positive test developed GVHD versus 10 of 25 recipients (40%) of marrow from donors with a negative test (p = 0.03). The previously reported risk for GVHD attributed to donor CMV antibodies increased the risk of GVHD due to donor HSV antibodies. Of 31 recipients of marrow from donors who were both HSV- and CMV-seropositive, 27 (85%) developed GVHD versus 11 of 22 recipients (50%) of marrow from HSV-seropositive but CMV-seronegative donors (p = 0.008).

Selectivity of Organic Products to Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae).

The selectivity of various entomopathogens and one insecticide (chlorpyrifos = positive control) to Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae) was evaluated in the laboratory, using the protocol established by the Working Group on "Pesticides and Beneficial Organisms" of the IOBC. The evaluated parameters were parasitism (%), adult emergence (%), and product repellency to the parasitoid when sprayed on host eggs prior to parasitism (free-choice and no-choice tests). Most of the studied entomopathogens (Bacillus thuringiensis var. kurstaki, Bacillus thuringiensis var. aizawai, Beauveria bassiana, Metarhizium anisopliae, and Trichoderma harzianum) had no effects on biological parameters and were classified as harmless to T. pretiosum. Emergence of parasitoids (progeny viability) was reduced, but remained above 90%, when host eggs were sprayed with Baculovirus anticarsia prior to parasitism in the free-choice test, and B. anticarsia was therefore considered harmless. Chlorpyrifos (positive control) caused high adult parasitoid mortality in all bioassays. While T. pretiosum and the tested entomopathogens may be used simultaneously in integrated pest management programs, the use of chlorpyrifos should be avoided.

Dissociation, childhood trauma, and ataque de nervios among Puerto Rican psychiatric outpatients.

OBJECTIVE: This study examined the relationships of dissociation and childhood trauma with ataque de nervios. METHOD: Forty Puerto Rican psychiatric outpatients were evaluated for frequency of ataque de nervios, dissociative symptoms, exposure to trauma, and mood and anxiety psychopathology. Blind conditions were maintained across assessments. Data for 29 female patients were analyzed. RESULTS: Among these 29 patients, clinician-rated dissociative symptoms increased with frequency of ataque de nervios. Dissociative Experiences Scale scores and diagnoses of panic disorder and dissociative disorders were also associated with ataque frequency, before corrections were made for multiple comparisons. The rate of childhood trauma was uniformly high among the patients and showed no relationship to dissociative symptoms and disorder or number of ataques. CONCLUSIONS: Frequent ataques de nervios may, in part, be a marker for psychiatric disorders characterized by dissociative symptoms. Childhood trauma per se did not account for ataque status in this group of female outpatients.

HLA antigens in patients with chronic inflammatory demyelinating polyneuropathy.

In a group of 52 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP), no significant associations were found with any of the HLA-A, B, C, DR or DQ antigens. No HLA association was found between the presence or absence of anti-neural antibodies or between the group of patients improving or not improving after intravenous immunoglobulin. These findings mean that we could not confirm results from the literature that suggest that CIDP is associated with the HLA-A1,B8,DR3 haplotype or--as recently was suggested--with the HLA-Cw7 or DR2 antigen.

Cell-mediated lympholysis studies in renal allograft recipients.

Cell-mediated lympholysis (CML) reactivity against the splenocytes of the kidney donor might be a good in vitro correlate of the homograft reaction. The present study was performed in an attempt to determine whether CML nonreactivity between unrelated donor-recipient combinations occur and, if so, under what conditions. We were able to show that CML nonreactivity occurs between unrelated donor-recipient combinations in 70% of the nonrejecting patients, whereas all of the rejecting patients were CML reactive. Patients with CML nonreactivity did clinically well more frequently than those that were CML reactive. The question as to whether or not such variables as HLA-A, B, and DR match and sex, the number of pretransplant blood transfusions, and the degree of presensitization, etc. predispose to the development of donor-specific CML nonreactivity was studied as well. Sex and compatibility for HLA-B antigens between donor and recipient might be such factors.

The effect of HLA matching on kidney graft survival in separate posttransplantation intervals.

The effect of matching for the HLA antigens has been well established as important in the prognosis of kidney grafts. By analyzing the effect of matching on first transplants from unrelated donors in specific intervals up to 3 years posttransplantation, we show that the effect of HLA-DR matching is strongest in the first 5 months following transplantation (relative risks of graft failure 1.31 and 1.77 for 1 and 2 HLA-DR mismatches, respectively, compared with no mismatches). For patients whose grafts remained functioning after 5 months, there was no significant further improvement in graft survival to 3 years (relative risks 1.16 and 0.98 for 1 and 2 HLA-DR mismatches, respectively, compared with no mismatches)--i.e., the gain in graft survival by matching for HLA-DR appears to be due to its influence in the first 5 months following transplantation. For HLA-B, the matching effect was evident both before and after 5 months (relative risks 1.11 and 1.27 for 1 and 2 HLA-B mismatches, respectively, compared with no mismatches and modelled as constant over the 3-year period), whereas no effect of HLA-A matching was evident in the period up to 3 years.

The impact of HLA-A matching on long-term survival of renal allografts.

An important contribution of HLA-A antigen matching in renal transplantation was reported initially, hut later publications showed a minor or absent role. We analyzed the contribution of HLA-A locus matching to graft survival in 17,672 first renal transplants from unrelated, nonliving donors. We show that an independent HLA-A matching effect still exists. Due to its relative weakness and late appearance, large numbers and longer follow-up periods are required. The HLA-A matching effect is a significant factor in first renal allograft survival up to 6 years after transplantation, with an increasing effect over time. This is in contrast to the strong, short-lived, effects of HLA-DR and -B matching, which can only be detected up to 6 months and 2 years after transplantation, respectively. A clear additive beneficial effect of HLA-A matching is shown in the group without B and DR mismatches. Therefore, prospective matching for the HLA-A antigens remains important for renal allograft survival.