Notes

Pore-forming alpha-hemolysin effectively improves the immunogenicity and also protecting usefulness involving necessary protein antigens.
High-volume online hemodiafiltration (HDF) has been reported to reduce the patient's mortality. However, achieving a high convection volume is challenging. In this prospective study, we investigated the feasibility of achieving high-volume HDF with ≥21 L substitution volume via modification of blood flow rate (BFR), needle size, and dialysis membrane. In 30 patients undergoing hemodialysis, we followed a stepwise protocol and gradually increased the BFR (280→300→330 ml/min; steps 1, 2, and 3) and needle size (16→15 G; step 4). After changing dialyzer surface area (1.8 m2 →2.5 m2 ), the BFR and needle size were similarly increased stepwise (steps 5, 6, 7, and 8). The mean substitution volume was 18.7 ± 2.2 L at step 1 and it significantly increased to 25.1 ± 2.6 L by step 8. A substitution volume of 21 L was achieved by 13.3% of patients in step 1 and by 96.7% after step 8. The substitution volume was higher for the dialyzer with a large surface area and for the larger needle (15 G). Between steps 1 and 8, the Kt/V and β2 microglobulin reduction ratios also improved significantly. High-volume HDF is feasible through a stepwise increase in the BFR, needle size, and surface area of the dialysis membrane.Cold atmospheric plasma (CAP) is an emerging technology for biomedical applications, exemplified by its antimicrobial and antineoplastic potentials. On the contrary, acidic fibroblast growth factor (aFGF) has been a long-standing potent mitogen for cells from various origins. In this study, we are the first to develop a multimodal treatment combining the aforementioned physicochemical and pharmacological treatments and investigated their individual and combined effects on wound healing, angiogenesis, neurogenesis, and osteogenesis. This work was performed at the tissue, cellular, protein, and gene levels, using histochemical staining, flow cytometry, ELISA, and PCR, respectively. Depending on the type of target tissue, various combinations of aforementioned methods were used. The results showed that the enhancement on would healing and angiogenesis by CAP and aFGF were synergistic. The former was manifested by increased murine fibroblast proliferation and reduced cutaneous tissue inflammation, whereas the latter by upregulated proangiogenic markers in vivo, for example, CD31, VEGF, and TGF-β, and downregulated antiangiogenic proteins in vitro, for example, angiostatin and angiopoietin-2, respectively. In addition, aFGF outperformed CAP during neurogenesis, which was evidenced by superior neurite outgrowth, while CAP exceeded aFGF in osteogenesis which was demonstrated by more substantial bone nodule formation. These novel findings not only support the fact that CAP and aFGF are both multipotent agents during tissue regeneration, but also highlight the potential of our multimodal treatment combining the individual advantages of CAP and aFGF. The versatile administration route, that is, topical and/or systemic, might further broaden its applications.
Insulin resistance is an under-recognised metabolic defect and cardiovascular risk factor in Type 1 diabetes. Whether metformin improves hepatic, muscle or adipose tissue insulin sensitivity has not been studied in adults with Type 1 diabetes. We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double-blind randomised, placebo-controlled trial to measure the effect of metformin on tissue-specific insulin resistance in adults with Type 1 diabetes.

We will study 40 adults aged 20-55years with Type 1 diabetes (HbA1c


≤

80mmol/mol [9.5%], fasting C-peptide <0.3nmol/L) and 20 age-, gender- and body mass index (BMI)-matched controls. Insulin sensitivity will be determined by the two-step hyperinsulinaemic-euglycaemic clamp method with deuterated glucose to document liver, muscle and adipose insulin sensitivity. Subjects with Type 1 diabetes will be randomised to metformin extended-release 1500mg daily or matched placebo for 26weeks. The primary outcome is change in hepatic insulin sensitivity, assessed by change in basal rate of appearance (Ra) of glucose and suppression of endogenous glucose production (EGP) during the low-dose stage of the clamp.

The INTIMET study is the first clinical trial to quantify the impact of metformin on liver, muscle and adipose insulin resistance in adults with Type 1 diabetes. This study may identify factors that predict an individual's response to metformin in Type 1 diabetes.

ACTRN12619001440112.
ACTRN12619001440112.Fifty-five clinicians who provided teletherapy to couples, partnerships, families, and kin networks during the first two months of the coronavirus pandemic responded to a survey about their most and least meaningful experiences. Reflexive thematic analysis indicated that the participants experienced adjustments to their schedule or routines, they used technology glitches to promote client growth, and they altered how they engaged clients. Participants noted shifts in their personal and relational dynamics. They reported feeling fatigued and resilient. Participants described their adaptability, gratitude, digital and relational connectivity, and an ability to reframe negative experiences into opportunities for growth.Adherence to medicines tends to be envisaged as a matter of actors' reasoned actions, though there is increasing emphasis on situating adherence as a practice materialised in everyday routines. Drawing on the qualitative interview accounts of Black African women living with HIV in London, UK, we treat adherence to HIV medicines as not only situated in the practices of the immediate and everyday but also relating to a hinterland of historical and social relations. We move from accounts which situate adherence as an embodied matter of affect in the present, to accounts which locate adherence as a condition of precarity, which also trace to enactments of time and place in the past. Adherence is therefore envisaged as a multiple and fluid effect which is made-up in-the-now and in relation to a hinterland of practices which locate elsewhere.
Ultrasound-targeted microbubble destruction (UTMD) has been widely applied to enhance chemotherapy of tumors, yet few studies have focused on the metastatic potential induced by UTMD. This study aimed to explore the metastasis of VX2 tumors after treatment with UTMD and chemotherapy.

Forty-four New Zealand rabbits bearing subcutaneous VX2 tumors were enrolled for the treatment of UTMD with chemotherapy. For UTMD, the tumors were insonated using two pulsing protocols of diagnostic ultrasound (DUS, VINNO and ECARE) with a mechanical index (MI) of 0.29-0.33, tone burst of 8.0 cycles, and frequencies of 3-4 MHz. A total dose of 2 mL SonoVue
was injected intermittently during 10 min UTMD exposure. Sodium hydroxide in vitro The combination therapy was treated using doxorubicin (DOX, 2 mg/kg) and DUS, while the tumors treated using DOX only served as the control. Tumor size was measured using the tumor volume formula. Survival time was observed until animal death or the end of the study (120 days). Specific organs (lung, liver, kidney, and brain) were removed for metastatic evaluation.

There were no statistical differences in overall metastasis classification and individual organ metastases among all groups (P>0.05). The tumor growth rate only showed inhibition on the 5
day (P<0.01). The survival time did not demonstrate any significant difference between UTMD and chemotherapy only (P>0.05).

UTMD using long pulse DUS with commercial microbubbles did not pose a risk of metastasis enhancement in DOX chemotherapy.
UTMD using long pulse DUS with commercial microbubbles did not pose a risk of metastasis enhancement in DOX chemotherapy.
Temporomandibular disorders (TMDs) are multifactorial, and high levels of stress seem to increase symptoms. The association with exposure to violence has not been explored in adolescent populations.

To examine the association of self-reported symptoms of temporomandibular pain and jaw dysfunction with child physical abuse, intimate partner violence, forced sexual intercourse, and bullying victimisation.

An epidemiological, cross-sectional, school-based study was conducted in Olinda, northeast Brazil. The sample comprised 2,431 adolescents aged 14-19years. TMD-related symptoms and exposure to violence were assessed with questions from the 3Q/TMD screener and queries on exposure to different forms of violence. Multilevel logistic regressions were conducted to evaluate how 3Q screen-positive responses are associated with self-reported exposure to violence.

Self-reported TMD-related symptoms had a prevalence of 40.5%. Significantly more females than males screened positive to all 3Q/TMD questions (p<.001). Adolescents experiencing intimate partner violence (p=.012) and bullying (p<.001) had significantly higher odds of 3Q positive responses than those who reported no exposure to violence. Significant associations of TMD-related symptoms with forced sexual intercourse (p=.014) and with bullying (p=.007) were observed.

Adolescents with self-reported symptoms of temporomandibular pain and jaw dysfunction were significantly more often exposed to some type of violence. The number of adolescents reporting TMD-related symptoms increased in a dose-response manner with the number of violence forms the individual had experienced.
Adolescents with self-reported symptoms of temporomandibular pain and jaw dysfunction were significantly more often exposed to some type of violence. The number of adolescents reporting TMD-related symptoms increased in a dose-response manner with the number of violence forms the individual had experienced.
The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations.

We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data.

A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age aemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.
Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.
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