Ceftriaxone for the Treatment of Chronic Bacterial Prostatitis: A Case Series and Literature Review

Chronic bacterial prostatitis is increasingly difficult to treat due to rising antimicrobial resistance limiting oral treatment options. In this case series, 11 men with CBP (including patients with urological comorbidities) due to multi-resistant E. coli were treated with once-daily ceftriaxone intravenously for 6 weeks. Nine patients were clinically cured at 3 months follow up. No early withdrawal of medication due to side effects occurred. A literature review was conducted to describe the prostate pharmacokinetics of ceftriaxone and its use in prostatic infection. In conclusion, ceftriaxone can be considered an appropriate treatment of chronic bacterial prostatitis.

Wind steadiness up to 35 km and its variability before the southwest monsoon onset and the withdrawal

This paper brings out mainly on the quantitative approach to delineate wind direction variability through Wind Steadiness Factor (WSF) - a single parameter which depends on height, wind speed and wind direction. This can be used as a prognostic parameter for the onset and withdrawal of south west monsoon (SW Monsoon) over Kerala. A brief sketch on wind climatology up to 35 km over TERLS (8° 32' N / 76° 52' E) is also discussed to have a background knowledge. From the derived WSF climatology, it is seen that the region between 12.5 km to 18 km is of highest WSF during the SW Monsoon due to the Tropical Easterly Jet (TEJ). Vertical variation of annual WSF has shown well demarcated four layered structure and the wind rose constructed for each layer provides the contribution of WSF attributed by the dominant direction for that particular layer. A WSF value was estimated for the region between 12.5 km to 18 km over Thiruvananthapuram for each available rawin profile [0530 and 1730 hrs (IST)] and inferred that an early incidence and maintenance of WSF well above 80% prior the SW Monsoon supports an early SW Monsoon onset and reverse for a late onset. A late/early WSF decrease from a value of 80% followed by systematic further decrease is associated with late/early withdrawal of the SW Monsoon.

Correlations Between the DMN and the Smoking Cessation Outcome of a Real-Time fMRI Neurofeedback Supported Exploratory Therapy Approach: Descriptive Statistics on Tobacco-Dependent Patients

The aim of this study was to explore the potential of default mode network (DMN) functional connectivity for predicting the success of smoking cessation in patients with tobacco dependence in the context of a real-time function al MRI (RT-fMRI) neurofeedback (NF) supported therapy. Fifty-four tobacco-dependent patients underwent three RT-fMRI-NF sessions including resting-state functional connectivity (RSFC) runs over a period of 4 weeks during professionally assisted smoking cessation. Patients were randomized into two groups that performed either active NF of an addiction-related brain region or sham NF. After preprocessing, the RSFC baseline data were statistically evaluated using seed-based ROI (SBA) approaches taking into account the smoking status of patients after 3 months (abstinence/relapse). The results of the real study group showed a widespread functional connectivity in the relapse subgroup (n = 10) exceeding the DMN template and mainly low correlations and anticorrelations in the within-seed analysis. In contrast, the connectivity pattern of the abstinence subgroup (n = 8) primarily contained the core DMN in the seed-to-whole-brain analysis and a left lateralized correlation pattern in the within-seed analysis. Calculated Multi-Subject Dictionary Learning (MSDL) matrices showed anticorrelations between DMN regions and salience regions in the abstinence group. Concerning the sham group, results of the relapse subgroup (n = 4) and the abstinence subgroup (n = 6) showed similar trends only in the within-seed analysis. In the setting of a RT-fMRI-NF-assisted therapy, a widespread intrinsic DMN connectivity and a low negative coupling between the DMN and the salience network (SN) in patients with tobacco dependency during early withdrawal may be useful as an early indicator of later therapy nonresponse.

Beta-Endorphin and Oxytocin in Patients with Alcohol Use Disorder and Comorbid Depression

Background: The neuropeptides β-endorphin and oxytocin are released into the bloodstream as hormones from the pituitary gland but also have an important function as neuroregulators in the forebrain. The blood levels of both polypeptides have been shown to reflect depressive symptoms. β-Endorphin, in particular, is also involved in abstinence from alcohol. Methods: The serum levels of β-endorphin and oxytocin were measured during the early withdrawal phase in patients with alcohol use disorder (AUD) with (N = 35) or without (N = 45) depressive comorbidity and compared with those in healthy volunteers (N = 23). In addition to comparing the groups, the study examined whether serum levels correlated with various psychometric measures of dependence, depression and aggression, as well as with clinical characteristics of dependence. Results: Both serum levels of beta-endorphin and oxytocin were significantly lower in patients than those in healthy controls (p = 0.011 for β-endorphin and p = 0.005 for oxytocin, Kruskal–Wallis test). In patients with depressive comorbidity, the significance was greatest (p = 0.005 for β-endorphin and p = 0.004 for oxytocin, U-test). There was no correlation with clinical or psychometric parameters (p > 0.05, Spearman test), but beta-endorphin levels did correlate significantly with physical aggression (p = 0.026, Spearman test). Conclusions: Serum levels of β-endorphin and oxytocin are lower in patients with AUD, particularly in those with depressive comorbidity. β-Endorphin levels correlated with physical aggression according to the Buss–Durkee (BDHI) estimates.

Examining opioid withdrawal scoring and adaptation of global scoring systems to male and female C57BL/6J mice

Opioid Use Disorder (OUD) is a chronic and relapsing psychiatric condition which is currently the leading cause of accidental death in the US. Symptoms of acute opioid withdrawal resemble a flu-like illness which is accompanied by a dysphoric state. Psychological comorbidities such as anxiety, depression, and disordered sleep can persist for months or years, well into the abstinence period. These symptoms are thought to drive further opioid intake in order to alleviate this unpleasant internal state. Many differences in OUD have been documented between male and female patients, with females at higher risk for relapse and overdose. This study sets out to characterize sex differences in symptoms and behavioral adaptations in mice during early withdrawal. Using our moderate dose, three-day precipitated withdrawal paradigm, we discovered significant effects of sex, time, and drug treatment on early withdrawal behaviors, locomotor activity, and gut motility in C57BL/6J mice. Here I will discuss previous methods of condensing behavioral phenotypes into one global withdrawal score, and propose a new methodology. This method increases the ability to detect nuanced effects and allows for more accurate translation across strain, sex, paradigm, and experimental context. Classification of opioid withdrawal-induced behavioral adaptations will allow for improved behavioral analysis of pharmacological manipulations, and investigations of brain circuitry involved in opioid withdrawal, as well as future screening of compounds with potential therapeutic benefit for the treatment of OUD.

Reflections after TWILIGHT study: a new era in secondary prevention without aspirin?

Dual antiplatelet therapy (DAPT) is mandatory in patients undergoing percutaneous coronary interventions (PCIs), but carries an increased bleeding risk which must be weighed over the expected antithrombotic benefit. In recent years, DAPT optimization strategy has been enriched by the concept of early withdrawal of aspirin (‘aspirin-free’ strategy). This strategy is supported by the modern advancements in pharmacological and procedural fields (i.e. the availability of P2Y12 receptor inhibitors with a concomitant ‘aspirin-like’ effect), the advocated use of pharmacological non-antiplatelet secondary prevention strategies (i.e. angiotensin-converting enzyme inhibitor, statins, beta-blockers), the use of modern stents and the increasingly widespread use of intra-coronary imaging techniques. In the last few years, five clinical trials (GLOBAL LEADERS, TWILIGHT, STOP-DAPT2, SMART CHOICE, TICO) and their own meta-analysis have been followed, aiming to evaluate the efficacy and safety of different ‘aspirin-free’ strategies. They showed that aspirin withdrawal (1–3 months after PCI), determines a consistent reduction of bleeding risk, without compromising efficacy endpoints. It resulted in a class IIa indication in the 2020 European Society of Cardiology Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation, which suggested the early withdrawal of aspirin in patients undergoing PCI and considered to be at low ischaemic and low bleeding risk, or at high bleeding risk.

Can we learn from hidden mistakes? Self-fulfilling prophecy and responsible neuroprognostic innovation

A self-fulfilling prophecy (SFP) in neuroprognostication occurs when a patient in coma is predicted to have a poor outcome, and life-sustaining treatment is withdrawn on the basis of that prediction, thus directly bringing about a poor outcome (viz. death) for that patient. In contrast to the predominant emphasis in the bioethics literature, we look beyond the moral issues raised by the possibility that an erroneous prediction might lead to the death of a patient who otherwise would have lived. Instead, we focus on the problematic epistemic consequences of neuroprognostic SFPs in settings where research and practice intersect. When this sort of SFP occurs, the problem is that physicians and researchers are never in a position to notice whether their original prognosis was correct or incorrect, since the patient dies anyway. Thus, SFPs keep us from discerning false positives from true positives, inhibiting proper assessment of novel prognostic tests. This epistemic problem of SFPs thus impedes learning, but ethical obligations of patient care make it difficult to avoid SFPs. We then show how the impediment to catching false positive indicators of poor outcome distorts research on novel techniques for neuroprognostication, allowing biases to persist in prognostic tests. We finally highlight a particular risk that a precautionary bias towards early withdrawal of life-sustaining treatment may be amplified. We conclude with guidelines about how researchers can mitigate the epistemic problems of SFPs, to achieve more responsible innovation of neuroprognostication for patients in coma.

Preclinical evidence to support repurposing everolimus for craving reduction during protracted drug withdrawal

Cue-elicited drug-craving is a cardinal feature of addiction that intensifies (incubates) during protracted withdrawal. In a rat model, these addiction-related behavioral pathologies are mediated, respectively, by time-dependent increases in PI3K/Akt1 signaling and reduced Group 1 metabotropic glutamate receptor (mGlu) expression, within the ventromedial prefrontal cortex (vmPFC). Herein, we examined the capacity of single oral dosing with everolimus, an FDA-approved inhibitor of the PI3K/Akt effector mTOR, to reduce incubated cocaine-craving and reverse incubation-associated changes in vmPFC kinase activity and mGlu expression. Rats were trained to lever-press for intravenous infusions of cocaine or delivery of sucrose pellets and then subjected to tests for cue-reinforced responding during early (3 days) or late (30–46 days) withdrawal. Rats were gavage-infused with everolimus (0–1.0 mg/kg), either prior to testing to examine for effects upon reinforcer-seeking behavior, or immediately following testing to probe effects upon the consolidation of extinction learning. Single oral dosing with everolimus dose-dependently blocked cocaine-seeking during late withdrawal and the effect lasted at least 24 h. No everolimus effects were observed for cue-elicited sucrose-seeking or cocaine-seeking in early withdrawal. In addition, everolimus treatment, following initial cue-testing, reduced subsequent cue hyper-responsivity exhibited observed during late withdrawal, arguing a facilitation of extinction memory consolidation. everolimus’ “anti-incubation” effect was associated with a reversal of withdrawal-induced changes in indices of PI3K/Akt1/mTOR activity, as well as Homer protein and mGlu1/5 expression, within the prelimbic (PL) subregion of the prefrontal cortex. Our results indicate mTOR inhibition as a viable strategy for interrupting heightened cocaine-craving and facilitating addiction recovery during protracted withdrawal.

Financial Literacy and the Early Withdrawal of Funds From Retirement Accounts

This study examined the association between financial literacy and the decision to withdraw funds from different types of retirement accounts before retirement. Data from the 2012 and 2015 National Financial Capability Study were used to investigate if financial literacy may potentially influence the decision to dissave from funds already set aside for retirement. The results showed that lower financial literacy appeared to increase the likelihood to retract funds saved for retirement, across different types of retirement accounts. The importance of financial literacy persisted, even after controlling for income shocks to personal finances, the availability of precautionary savings as an alternative source of funding, and an extensive set of demographic variables.