Higher frequency of administration of biotherapic T. cruzi 17DH decreases parasitemia and increases survival in mice infected with Trypanosoma cruzi

Introduction: The study of the effect of different ways of treatment using highly diluted substances is rare in the literature. Some authors consider the dose irrelevant, justifying that the action of the medication highly diluted is qualitative [1-3]. Others emphasize the importance of quantity and frequency of administration of the highly diluted substance for a successful treatment [4,5]. The model of murine infection by T. cruzi is widely studied and it is an excellent tool to study the effect of highly diluted substances. Aim: To evaluate, in vivo, the effect of different amounts and frequency of administration of the biotherapic 17 dH T. cruzi in the evolution of the parasitemia curve and survival of mice infected with Trypanosoma cruzi. Materials and methods: A blind randomised controlled trial was performed, using 30 swiss male mice, aged 28 days, divided into groups according to treatment: CONTROL - mice treated with 7% water-alcohol solution diluted in water given ad libitum in an amber bottle; GAVAGE – mice treated with medication highly diluted 17 DH T. cruzi from 4 th to 9 th day of infection by gavage; WATER - mice treated with highly diluted medication 17 DH T. cruzi in water ad libitum offered in an amber bottle until the end of the study period. The groups were infected with the Y strain of T. cruzi, intraperitoneal, 1400 blood trypomastigotes. The medicines was handled according to the Brazilian Homeopathic Pharmacopoeia [6] with microbiological test according to RDC n°. 67 and in vivo biological risk. Parasitemic curve was determined by daily counting of the parasites [7], the total parasitemia, peak parasites and survival. Data were compared using the BioEstat 5.0, ANOVA, with significance of 5%. The experiment was approved under the protocol n° 030/2008 - Ethics in Animal Experimentation of the Universidade Estadual de Maringá. Results: Animals treated with the medication highly diluted in water had lower level of total parasitemia and a lower peak of parasites compared to animals treated by gavage, or control group of infection (p = 0.0103 p = 0.0008). In the group treated by gavage both the total parasitemia and the peak of parasites were higher than the control group. Survival was greater in animals treated with biotherapic diluted with water (p = 0.0003) and by gavage (p = 0.0016) when compared with the control group. Among the different ways of treatment the use of medication diluted in water increased the survival of animals (p = 0.0013). The treatment by gavage once a day until the 9th day of infection increase the parasitemia and survival. The medication diluted in water showed better results with significant reduction of parasitemia and an increase of survival. This result may be related to the frequency with which the medication diluted in water was ingested by each animal, and the lower stress that this form of administration provides the animals. Figure 1: Parasitemic curve of animals infected with Y strain of T. cruzi and treated with medication highly diluted 17DH T. cruzi. CONTROL: mice treated with alcohol 7%; GAVAGE: treated with medication highly diluted 17DH T. cruzi by gavage; WATER: treated with medication highly diluted 17dH T. cruzi in water. Conclusion: There is a difference in the effect of the medication highly diluted depending on the way of treatment used. For mice, the use of drug diluted in water offered frequently, results in better benefits. The clinical use of these results in humans, should consider the allometric system medication dosage which takes into account the metabolic rate of each organism.

Outcome of Critically Ill COVID-19 Patients According to the Setting of Corticosteroid Initiation—A Retrospective Observational Cohort Study

(1) Background: Corticosteroids lower 28-day all-cause mortality in critically ill COVID-19 patients. However, the outcome of COVID-19 patients referred to the intensive care unit (ICU) for respiratory deterioration despite corticosteroids initiated during hospitalization before ICU admission has been poorly investigated. Our objective was to determine survival according to corticosteroid initiation setting. (2) Methods: We conducted a cohort study including all successive critically ill COVID-19 patients treated with corticosteroids and managed in our ICU. We compared survival, whether corticosteroids were initiated before (Cb-group) or after ICU admission (Ca-group), using a propensity score matching. (3) Results: Overall, 228 patients (67 years (56–74); 168M/60F; invasive mechanical ventilation on admission, 17%) were included with 63 patients in the Cb-group and 165 patients in the Ca-group. Survival to hospital discharge was 43% versus 69%, respectively (p = 0.001). In a multivariable analysis, factors associated with death were age (odds ratio, 1.07; 95%-confidence interval, (1.04–1.11); p < 0.0001), the sequential organ failure assessment (SOFA) score on ICU admission (1.30 (1.14–1.50); p = 0.0001) and corticosteroid initiation before ICU admission (2.64 (1.30–5.43); p = 0.007). No significant differences in outcome related to corticosteroid regimen were found. (4) Conclusions: Critically ill COVID-19 patients transferred to the ICU with deterioration despite corticosteroids initiated before admission have a less favorable outcome than patients receiving corticosteroids initiated after ICU admission.

Group Borrowing : Microfinance-Tontine Sustainable Co-Existence. Case Of Cameroon

This paper uses a case study approach to examine the role of group account in Microfinance institutions on tontine's survival. The research investigates on the origin of funds deposited in group accounts, and its importance to group members. The collection of respondents’ perceptions will contribution to promote digital-group account – accessible both on apps and handset – for the group’s benefit. We interviewed ten participants coming from the critical stakeholders of rural finance in the community of Balessing in the west region of Cameroon. We performed a textual and content analysis of the qualitative data collected. The results showed that group accounts contribute to the financial, managerial and social development of tontine group – factors indispensable for strong cohesion and group survival. Moreover, group accounts also benefit microfinance institutions by contributing to their growth and development. From the results mentioned above, we made recommendations to consolidation the link between microfinance institutions and tontine groups through group accounts.

The Game of Poker Chips, Dominoes and Survival

The Game of Poker Chips, Dominoes and Survival fosters team building and high level cooperation in large groups, and is a tool applied in management training exercises. Each player, initially given two colored poker chips, is allowed to make exchanges with the game coordinator according to two rules, and must secure a domino before time is called in order to ‘survive’. Though the rules are simple, it is not evident by their form that the survival of the entire group requires that they cooperate at a high level. From the point of view of the game coordinator, the di culty of the game for the group can be controlled not only by the time limit, but also by the initial distribution of chips, in a way we make precise by a time complexity type argument. That analysis also provides insight into good strategies for group survival, those taking the least amount of time. In addition, coordinators may also want to be aware of when the game is ‘solvable’, that is, when their initial distribution of chips permits the survival of all group members if given su cient time to make exchanges. It turns out that the game is solvable if and only if the initial distribution contains seven chips that have one of two particular color distributions. In addition to being a lively game to play in management training or classroom settings, the analysis of the game after play can make for an engaging exercise in any discrete mathematics course to give a basic introduction to elements of game theory, logical reasoning, number theory and the computation of algorithmic complexities.

Older age and varus alignment lead to early failure in treating patellofemoral osteoarthritis with Fulkerson osteotomy

Background: It is unclear the risk factors for the failure of modified Fulkerson osteotomy. Methods: We retrospectively reviewed 40 patients who underwent the modified Fulkerson osteotomy from 1998 to 2015. There were 4 males and 36 females. The mean age of the study group was 50.2 ± 11.2 years. We used standard anteriorization measuring 10–15 mm and medialization measuring 10 mm while maintaining an intact periosteal sleeve. Results: Both the patellofemoral angle and the congruence angle improved significantly after 5.9 years. Preoperatively, the mean preoperative Lysholm score was 56.12, and the Knee Society score was 60.52. At the final follow-up, these scores improved significantly to 88.75 and 86.49, respectively. However, eight patients (20%) underwent total knee arthroplasty in the follow-up period, five of whom underwent the operation within 5 years. Comparing the survival and non-survival groups, there was a significant difference of an older age in the TKA conversion group (survival: 48.3 ± 11.1; non-survival: 57.8 ± 8.7, p = 0.03). For knee alignment, the non-survival group had a mean valgus femorotibial angle of 1.8° ± 4.9° preoperatively, and the survival group had a mean valgus angle of 6.4° ± 4.5° ( p = 0.03). Conclusions: we found that patients with older age and those with varus alignment have an increased risk of deteriorated medial femorotibial cartilage.

Clinicopathologic and Prognostic Association of GRP94 Expression in Colorectal Cancer with Synchronous and Metachronous Metastases

Patients with advanced colorectal cancer (CRC) with distant metastases have a poor prognosis. We evaluated the clinicopathological relevance of GRP94 expression in these cases. The immunohistochemical expression of GRP94 was studied in 189 CRC patients with synchronous (SM; n = 123) and metachronous metastases (MM; n = 66), using tissue microarray; the association between GRP94 expression, outcome, and tumor-infiltrating lymphocytes (TILs) was also evaluated. GRP94 was expressed in 64.6% (122/189) patients with CRC; GRP94 positivity was found in 67.5% and 59.1% patients with SM and MM, respectively. In the SM group, high GRP94 expression was more common in patients with a higher density of CD4+ TILs (p = 0.002), unlike in the MM group. Survival analysis showed that patients with GRP94 positivity had significantly favorable survival (p = 0.030); after multivariate analysis, GRP94 only served as an independent prognostic factor (p = 0.034; hazard ratio, 0.581; 95% confidence interval, 0.351–0.961) in the SM group. GRP94 expression was detected in 49.4% of metastatic sites and showed significant heterogeneity between primary and metastatic lesions (p = 0.012). GRP94 is widely expressed in CRC with distant metastases; its expression was associated with favorable prognosis in the SM group, unlike in the MM group.

Long-term outcomes in children with absent pulmonary valve syndrome: it is not just fixing the heart

Objective Absent pulmonary valve syndrome (APV) is a rare condition usually associated with tetralogy of Fallot (TOF). Some infants develop respiratory failure from bronchial compression and the long-term neurodevelopmental outcome is unknown. We aimed to investigate the outcomes of APV and the need for long-term ventilation (LTV). Design, patients and setting Retrospective single-centre review of patients diagnosed with APV between 2007 and 2017. Outcome measures Survival, neurological disability and postoperative LTV (≥3 months of non-invasive or invasive respiratory support). Results Thirty patients were identified, 22 (73%) of whom were prenatally diagnosed. Pregnancy was discontinued in one patient, while in utero death occurred in three. One was lost to follow-up. Of the remaining 25 liveborn, 21 had the classic TOF/APV. One baby died immediately after birth, while two patients had palliative care due to severe airway compression and inability to wean ventilation support. Surgical repair was performed in 21 of the 25 (84%) liveborn, with one awaiting surgery. Of those undergoing surgery, two patients died: one during surgery and the other due to severe airway malacia 5 months postsurgery. In the surgical group survival from birth at 1 and 5 years was 89% (95% CI 75% to 100%). Six (30%) patients required LTV postoperatively; all had surgery within the first 6 months of life. Learning and/or other physical difficulties were evident in 63%. Conclusions Majority of patients with APV are diagnosed antenatally. A third of those operated required LTV and over half had learning and/or other physical difficulties. Prospective studies are needed to identify prenatal factors that predict postnatal outcomes so parents can be counselled appropriately.

A Biopsychosocial Approach to Understanding Panic Buying: Integrating Neurobiological, Attachment-Based, and Social-Anthropological Perspectives

The global COVID-19 pandemic has focused the attention of researchers, civil authority and the general public on the phenomenon of “panic buying,” characterized by the excessive purchase of specific materials—particularly food and hygiene-related products—in anticipation of an expected shortage. This phenomenon has been well-documented in response to several natural and man-made disasters, but its global scope and severity in the context of COVID-19 are unprecedented. This response can negatively impact health, food security, and disease prevention efforts. Attempts to modify such behaviors are more likely to succeed if they are based on insights from both the biomedical and the social sciences. From a biological perspective, the phenomenological overlap between panic buying and psychological disorders such as hoarding disorder and compulsive buying raises the possibility of a shared neurobiological underpinning. Evolutionary models suggest that these behaviors represent an attempt to enhance individual and group survival in the face of a threatened scarcity of resources. These phenomena may be influenced by specific genetic variants which are also implicated in hoarding-related psychological disorders. From a psychological perspective, attachment theory provides a conceptual framework that serves as a bridge between prior life adversity, current deprivation, and an increased attachment to material objects. Such a framework is of relevance when considering panic buying during the COVID-19 pandemic, which has been associated with significant disruptions in attachment bonds. From a social-anthropological perspective, hoarding and related behaviors have been associated with social exclusion and rejection, as well a lack of social support. These risk factors have affected large sections of the general population in the context of the COVID-19 pandemic and the governmental responses to it. This perspective also emphasizes the symbolic significance of the hoarded objects themselves. In this paper, an attempt is made to integrate these three perspectives and thereby formulate a biopsychosocial model of panic buying in response to this global health crisis. The existing scientific literature on panic buying is examined in the light of this model. Finally, suggestions are proposed as to how this model might inform social strategies aimed at preventing or reducing panic buying.