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Nevin Manimala Statistics

Phage-Antibiotic Synergy Inhibited by Temperate and Chronic Virus Competition

Bull Math Biol. 2022 Mar 22;84(5):54. doi: 10.1007/s11538-022-01006-6.

ABSTRACT

As antibiotic resistance grows more frequent for common bacterial infections, alternative treatment strategies such as phage therapy have become more widely studied in the medical field. While many studies have explored the efficacy of antibiotics, phage therapy, or synergistic combinations of phages and antibiotics, the impact of virus competition on the efficacy of antibiotic treatment has not yet been considered. Here, we model the synergy between antibiotics and two viral types, temperate and chronic, in controlling bacterial infections. We demonstrate that while combinations of antibiotic and temperate viruses exhibit synergy, competition between temperate and chronic viruses inhibits bacterial control with antibiotics. In fact, our model reveals that antibiotic treatment may counterintuitively increase the bacterial load when a large fraction of the bacteria are antibiotic resistant, and both chronic and temperate phages are present.

PMID:35316421 | DOI:10.1007/s11538-022-01006-6

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Nevin Manimala Statistics

Leftward and Posterior Deviation of the Septum Primum Predicts Morbidity in Patients with Hypoplastic Left Heart Syndrome

Pediatr Cardiol. 2022 Mar 22. doi: 10.1007/s00246-022-02860-w. Online ahead of print.

ABSTRACT

Leftward posterior deviation of the atrial septum primum (LDSP) has been reported in up to 64% of patients with hypoplastic left heart syndrome (HLHS) but there are no published data on its impact on neonatal outcomes. We reviewed the prevalence of LDSP and its correlation with neonatal outcomes in our institution. This was a single-center retrospective study of neonates with HLHS from 2001 to 2019. Echocardiograms were reviewed and the presence or absence of LDSP was noted. To quantify the degree of deviation in patients with LDSP, a new measurement, the deviation index (DI) was calculated using both the subcostal long and short-axis views. Of ninety-four patients with HLHS, fifty-seven (61%) patients were noted to have LDSP. There was no statistically significant difference in gestational age (GA), birth weight (BW), or mortality between patients with and without LDSP. Patients with LDSP had an increased incidence of unplanned reoperation (p < 0.01), post-operative cardiac catheterization (p < 0.05), and post-operative infection (p < 0.05). After correction for GA, BW, HLHS subtype, and type of surgery, LDSP predicted reoperation (OR = 3.6, p < 0.01), catheterization (OR = 2.7, p = 0.05), and infection (OR = 3.4, p < 0.05). Higher degree of deviation predicted reoperation (DI > 0.17), catheterization (DI > 0.07), and infection (DI > 0.12). There was excellent inter-observer reproducibility of the DI (ICCabsolute-agreement = 0.82, ICCconsistency = 0.90). Patients with LDSP have a higher prevalence of post-operative morbidity. The degree of deviation was found to be predictive of post-operative complications. Pre-operative echocardiographic evaluation of LDSP in patients with HLHS may be helpful in risk stratification and counseling.

PMID:35316357 | DOI:10.1007/s00246-022-02860-w

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Nevin Manimala Statistics

Baseline [18F]FDG PET/CT may predict the outcome of newly diagnosed follicular lymphoma in patients managed with initial “watch-and-wait” approach

Eur Radiol. 2022 Mar 22. doi: 10.1007/s00330-022-08624-7. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate if baseline [18F]FDG PET/CT can predict the outcome of follicular lymphoma (FL) in patients managed with an initial “watch-and-wait” approach.

METHODS: Thirty-eight newly diagnosed FL patients who were managed with an initial “watch-and-wait” approach and undergone baseline [18F]FDG PET/CT were retrospectively enrolled. The standard uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of FL lesions were measured on PET/CT. Patients were followed up for at least 24 months or until initiation of FL therapy. The endpoint was the time to initiation of lymphoma treatment (TLT).

RESULTS: After a median follow-up of 28 months (range 3-94 months), lymphoma treatment was initiated in 21/38 (55.3%) patients (median 15 months, range 3-51 months). Patients with TLT < 24 months showed SUVmax and TLG values significantly higher than those with TLT ≥ 24 months (p < 0.05). Receiver operating characteristic analysis demonstrated cutoff values of SUVmax > 9.5, MTV > 90.62 ml, and TLG > 144.96 SUVbw*ml were optimal for predicting TLT < 24 months. Kaplan-Meier analysis showed SUVmax > 9.5, MTV > 90.62 ml, and TLG > 144.96 SUVbw*ml had statistically significant correlations with shorter TLT (p < 0.01). Lymph node regions ≥ 3 and lymph nodes > 3 cm had almost significance (p < 0.1). In multivariate analysis, SUVmax > 9.5 (HR 3.2 [95% CI 1.1-9.2], p = 0.033) and TLG > 144.96 SUVbw*ml (HR 9.3 [95% CI 1.8-47.7], p = 0.008) were demonstrated to be independent predictive factors for shorter TLT.

CONCLUSIONS: Metabolic indices (SUVmax and TLG) of baseline [18F]FDG PET/CT could predict the outcome independently in FL patients under an initial “watch-and-wait” approach.

KEY POINTS: • “Watch-and-wait” approach is part of the overall treatment plan in asymptomatic patients with low tumor burden FL. However, the time to initiation of active treatment varies from months to years. • In our retrospective study of 38 patients with FL managed with an initial “watch-and-wait” approach, the SUVmax and TLG were demonstrated to be independent predictive factors for time to initiation of FL treatment. • Baseline [18F]FDG PET/CT may help to better select patients with FL who are most likely to benefit from “watch-and-wait” management.

PMID:35316362 | DOI:10.1007/s00330-022-08624-7

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Nevin Manimala Statistics

Motivation(s) from control: response-effect contingency and confirmation of sensorimotor predictions reinforce different levels of selection

Exp Brain Res. 2022 Mar 22. doi: 10.1007/s00221-022-06345-3. Online ahead of print.

ABSTRACT

Humans and other animals live in dynamic environments. To reliably manipulate the environment and attain their goals they would benefit from a constant modification of motor-responding based on responses’ current effect on the current environment. It is argued that this is exactly what is achieved by a mechanism that reinforces responses which have led to accurate sensorimotor predictions. We further show that evaluations of a response’s effectiveness can occur simultaneously, driven by at least two different processes, each relying on different statistical properties of the feedback and affecting a different level of responding. Specifically, we show the continuous effect of (a) a sensorimotor process sensitive only to the conditional probability of effects given that the agent acted on the environment (i.e., action-effects) and of (b) a more abstract judgement or inference that is also sensitive to the conditional probabilities of occurrence of feedback given no action by the agent (i.e., inaction-effects). The latter process seems to guide action selection (e.g., should I act?) while the former the manner of the action’s execution. This study is the first to show that different evaluation processes of a response’s effectiveness influence different levels of responding.

PMID:35316354 | DOI:10.1007/s00221-022-06345-3

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Nevin Manimala Statistics

Psoriasis comorbidities in Germany: A population-based study on spatiotemporal variations

PLoS One. 2022 Mar 22;17(3):e0265741. doi: 10.1371/journal.pone.0265741. eCollection 2022.

ABSTRACT

Psoriasis is a chronic disease with high impact on patients’ health and their quality of life. Psoriasis often occurs along with other comorbidities, but it is not yet clear what role the comorbidities play in regional psoriasis prevalence. This study investigates the temporal and regional variation of the psoriasis comorbidities diabetes mellitus type II, obesity, hypertension, affective disorders in Germany and their association with psoriasis prevalence. This analysis based on the population set of ambulatory claims data (2010-2017) of the statutory health insurance (SHI) in Germany (approx. 70.3 million people in 2017). Psoriasis comorbidities rates were determined on county level. We performed descriptive spatiotemporal analyses of psoriasis comorbidity prevalence rates. In addition, we identified and compared spatial clusters and examined regional variations using spatial statistical methods. The results show strong regional variations (northeast to south gradient) and an increasing psoriasis prevalence (max. 28.8%) within the observation period. Considering the comorbidities, results indicate comparable spatial prevalence patterns for diabetes mellitus type II, obesity and hypertension. This means that the highest prevalence of comorbidities tends to be found where the psoriasis prevalence is highest. The spatiotemporal cluster analyses could once again confirm the results. An exception to this is to be found in the case of affective disorders with different spatial patterns. The results of the studies show the first spatiotemporal association between psoriasis prevalence and comorbidities in Germany. The causalities must be investigated in more detail in order to be able to derive measures for improved care.

PMID:35316303 | DOI:10.1371/journal.pone.0265741

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Nevin Manimala Statistics

Baseline situational analysis in Bangladesh, Jordan, Paraguay, the Philippines, Ukraine, and Zimbabwe for the WHO Special Initiative for Mental Health: Universal Health Coverage for Mental Health

PLoS One. 2022 Mar 22;17(3):e0265570. doi: 10.1371/journal.pone.0265570. eCollection 2022.

ABSTRACT

INTRODUCTION: Mental, neurological and substance use conditions lead to tremendous suffering, yet globally access to effective care is limited. In line with the 13th General Programme of Work (GPW 13), in 2019 the World Health Organization (WHO) launched the WHO Special Initiative for Mental Health: Universal Health Coverage for Mental Health to advance mental health policies, advocacy, and human rights and to scale up access to quality and affordable care for people living with mental health conditions. Six countries were selected as ‘early-adopter’ countries for the WHO Special Initiative for Mental Health in the initial phase. Our objective was to rapidly and comprehensively assess the strength of mental health systems in each country with the goal of informing national priority-setting at the outset of the Initiative.

METHODS: We used a modified version of the Program for Improving Mental Health Care (PRIME) situational analysis tool. We used a participatory process to document national demographic and population health characteristics; environmental, sociopolitical, and health-related threats; the status of mental health policies and plans; the prevalence of mental disorders and treatment coverage; and the availability of resources for mental health.

RESULTS: Each country had distinct needs, though several common themes emerged. Most were dealing with crises with serious implications for population mental health. None had sufficient mental health services to meet their needs. All aimed to decentralize and deinstitutionalize mental health services, to integrate mental health care into primary health care, and to devote more financial and human resources to mental health systems. All cited insufficient and inequitably distributed specialist human resources for mental health as a major impediment.

CONCLUSIONS: This rapid assessment facilitated priority-setting for mental health system strengthening by national stakeholders. Next steps include convening design workshops in each country and initiating monitoring and evaluation procedures.

PMID:35316294 | DOI:10.1371/journal.pone.0265570

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Nevin Manimala Statistics

Are the forearm muscles excited equally in different, professional piano players?

PLoS One. 2022 Mar 22;17(3):e0265575. doi: 10.1371/journal.pone.0265575. eCollection 2022.

ABSTRACT

BACKGROUND AND OBJECTIVES: Professional pianists tend to develop playing-related musculoskeletal disorders mostly in the forearm. These injuries are often due to overuse, suggesting the existence of a common forearm region where muscles are often excited during piano playing across subjects. Here we use a grid of electrodes to test this hypothesis, assessing where EMGs with greatest amplitude are more likely to be detected when expert pianists perform different excerpts.

METHODS: Tasks were separated into two groups: classical excerpts and octaves, performed by eight, healthy, professional pianists. Monopolar electromyograms (EMGs) were sampled with a grid of 96 electrodes, covering the forearm region where hand and wrist muscles reside. Regions providing consistently high EMG amplitude across subjects were assessed with a non-parametric permutation test, designed for the statistical analysis of neuroimaging experiments. Spatial consistency across trials was assessed with the Binomial test.

RESULTS: Spatial consistency of muscle excitation was found across subjects but not across tasks, confining at most 20% of the electrodes in the grid. These local groups of electrodes providing high EMG amplitude were found at the ventral forearm region during classical excerpts and at the dorsal region during octaves, when performed both at preferred and at high, playing speeds.

DISCUSSION: Our results revealed that professional pianists consistently load a specific forearm region, depending on whether performing octaves or classical excerpts. This spatial consistency may help furthering our understanding on the incidence of playing-related muscular disorders and provide an anatomical reference for the study of active muscle loading in piano players using surface EMG.

PMID:35316295 | DOI:10.1371/journal.pone.0265575

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Amino acids versus magnesium sulfate infusion for controlling postoperative shivering in patients undergoing percutaneous nephrolithotomy surgery: a randomized clinical trial

Minerva Anestesiol. 2022 Mar 22. doi: 10.23736/S0375-9393.22.16237-1. Online ahead of print.

ABSTRACT

BACKGROUND: General anesthetics disrupt the thermoregulatory mechanisms by reducing vasoconstriction and shivering thresholds. Postoperative shivering is a challenging anesthesia-related complication with an incidence range of 20%-70%. Amino acids that induce thermogenesis and magnesium sulfate are centrally acting mechanisms that could minimize shivering. Thus, this trial was designed to compare the effect of amino acid versus magnesium sulfate infusion on postoperative shivering in patients undergoing elective percutaneous nephrolithotomy (PCNL) surgery under general anesthesia.

METHODS: Eighty adults, American Society of Anesthesiologists I and II patients, were randomly assigned into one of two groups. Group A received general anesthesia and perioperative IV amino acid infusion. Group M received general anesthesia and perioperative IV magnesium sulfate infusion.

RESULTS: There was a statistically significant difference in shivering score, which was lower in group A than M (0.8 ± 1.1 versus 1.5 ± 1.3; P-value= 0.01). The incidence of postoperative shivering was lower in group A [4 (10%)] versus [11 (27.5%)] in group M. A less decrease in the core intraoperative temperature (Celsius) was observed in group A than in group M (35.5 ± 0.2 versus 35.1 ± 0.2; respectively, P < 0.001) and at the end of surgery (36.1 ± 0.3 versus 35.7 ± 0.3; respectively, P < 0.001).

CONCLUSIONS: Perioperative amino acids infusion is more effective and better tolerated than magnesium sulfate in preventing postoperative shivering in patients undergoing percutaneous nephrolithotomy surgery. Cost effectiveness should be kept in mind, and amino acids infusion should be reserved in high-risk surgeries for shivering.

PMID:35315622 | DOI:10.23736/S0375-9393.22.16237-1

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Nevin Manimala Statistics

A Multi-Center, Double-Blind Randomized Controlled Phase III Clinical Trial to Evaluate the Antiviral Activity and Safety of DA-2802 (Tenofovir Disoproxil Orotate) and Viread (Tenofovir Disoproxil Fumarate) in Chronic Hepatitis B Patients

J Korean Med Sci. 2022 Mar 21;37(11):e92. doi: 10.3346/jkms.2022.37.e92.

ABSTRACT

BACKGROUND: Tenofovir disoproxil fumarate (TDF, Viread®) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF.

METHODS: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated.

RESULTS: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was -5.13 ± 1.40 in the DA-2802 group and -4.97 ± 1.40 log10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity.

CONCLUSION: DA-2802 is considered an effective and safe treatment for patients with CHB.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967939.

PMID:35315603 | DOI:10.3346/jkms.2022.37.e92

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Understanding modulations of lipid mediators in cancer using a murine model of carcinomatous peritonitis

Cancer Med. 2022 Mar 22. doi: 10.1002/cam4.4699. Online ahead of print.

ABSTRACT

BACKGROUND: Numerous studies have investigated the possible involvement of eicosanoids, lysophospholipids, and sphingolipids in cancer. We considered that comprehensive measurement of these lipid mediators might provide a better understanding of their involvement in the pathogenesis of cancer. In the present study, we attempted to elucidate the modulations of sphingolipids, lysophospholipids, diacyl-phospholipids, eicosanoids, and related mediators in cancer by measuring their levels simultaneously by a liquid chromatography-mass spectrometry method in a mouse model of carcinomatous peritonitis.

METHODS: We investigated the modulations of these lipids in both ascitic fluid and plasma specimens obtained from Balb/c mice injected intraperitoneally with Colon-26 cells, as well as the modulations of the lipid contents in the cancer cells obtained from the tumor xenografts.

RESULTS: The results were as follows: the levels of sphingosine 1-phosphate were increased, while those of lysophosphatidic acid (LysoPA), especially unsaturated long-chain LysoPA, tended to be increased, in the ascitic fluid. Our findings suggested that ceramides, sphingomyelin, and phosphatidylcholine, their precursors, were supplied by both de novo synthesis and from elsewhere in the body. The levels of lysophosphatidylserine (LysoPS), lysophosphatidylinositol, lysophosphatidylglycerol, and lysophosphatidylethanolamine were also increased in the ascitic fluid, while those of phosphatidylserine (PS), a precursor of LysoPS, were markedly decreased. The levels of arachidonic acid derivatives, especially PGE2-related metabolites, were increased, while the plasma levels of eicosanoids and related mediators were decreased. Comprehensive statistical analyses mainly identified PS in the ascitic fluid and eicosanoids in the plasma as having highly negative predictive values for cancer.

CONCLUSIONS: The results proposed many unknown associations of lipid mediators with cancer, underscoring the need for further studies. In particular, the PS/LysoPS pathway could be a novel therapeutic target, and plasma eicosanoids could be useful biomarkers for cancer.

PMID:35315587 | DOI:10.1002/cam4.4699