CDDO regulates central and peripheral sensitization to attenuate post-herpetic neuralgia by targeting TRPV1/PKC-δ/p-Akt signals.

Postherpetic neuralgia (PHN) is a notorious neuropathic pain featuring persistent profound mechanical hyperalgesia with significant negative impact on patients' life quality. CDDO can regulate inflammatory response and programmed cell death. Its derivative also protects neurons from damages by modulating microglia activities. As a consequence of central and peripheral sensitization, applying neural blocks may benefit to minimize the risk of PHN. This study aimed to explore whether CDDO could generate analgesic action in a PHN-rats' model. The behavioural test was determined by calibrated forceps testing. The number of apoptotic neurons and degree of glial cell reaction were assessed by immunofluorescence assay. Activation of PKC-δ and the phosphorylation of Akt were measured by western blots. CDDO improved PHN by decreasing TRPV1-positive nociceptive neurons, the apoptotic neurons, and reversed glial cell reaction in adult rats. It also suppressed the enhanced PKC-δ and p-Akt signalling in the sciatic nerve, dorsal root ganglia (DRG) and spinal dorsal horn. Our research is the promising report demonstrating the analgesic and neuroprotective action of CDDO in a PHN-rat's model by regulating central and peripheral sensitization targeting TRPV1, PKC-δ and p-Akt. It also is the first study to elucidate the role of oligodendrocyte in PHN.

Bone morphogenetic protein 4 derived from the cerebrospinal fluid in patients with postherpetic neuralgia induces allodynia via the crosstalk between microglia and astrocyte.

INTRODUCTION: During postherpetic neuralgia (PHN), the cerebral spinal fluid (CSF) possesses the capability to trigger glial activation and inflammation, yet the specific changes in its composition remain unclear. Recent findings from our research indicate elevations of central bone morphogenetic protein 4 (BMP4) during neuropathic pain (NP), serving as an independent modulator of glial cells. Herein, the aim of the present study is to test the CSF-BMP4 expressions and its role in the glial modulation in the process of PHN. METHODS: CSF samples were collected from both PHN patients and non-painful individuals (Control) to assess BMP4 and its antagonist Noggin levels. Besides, intrathecal administration of both CSF types was conducted in normal rats to evaluate the impact on pain behavior, glial activity, and inflammation.; Additionally, both Noggin and STAT3 antagonist-Stattic were employed to treat the PHN-CSF or exogenous BMP4 challenged cultured astrocytes to explore downstream signals. Finally, microglial depletion was performed prior to the PHN-CSF intervention so as to elucidate the microglia-astrocyte crosstalk. RESULTS: BMP4 levels were significantly higher in PHN-CSF compared to Control-CSF (P < 0.001), with a positive correlation with pain duration (P < 0.05, r = 0.502). Comparing with the Control-CSF producing moderate paw withdrawal threshold (PWT) decline and microglial activation, PHN-CSF further exacerbated allodynia and triggered both microglial and astrocytic activation (P < 0.05). Moreover, PHN-CSF rather than Control-CSF evoked microglial proliferation and pro-inflammatory transformation, reinforced iron storage, and activated astrocytes possibly through both SMAD159 and STAT3 signaling, which were all mitigated by the Noggin application (P < 0.05). Next, both Noggin and Stattic effectively attenuated BMP4-induced GFAP and IL-6 upregulation, as well as SMAD159 and STAT3 phosphorylation in the cultured astrocytes (P < 0.05). Finally, microglial depletion diminished PHN-CSF induced astrogliosis, inflammation and endogenous BMP4 expression (P < 0.05). CONCLUSION: Our study highlights the role of CSF-BMP4 elevation in glial activation and allodynia during PHN, suggesting a potential therapeutic avenue for future exploration.

The implementation of disaster preparedness training integration model based on Public Health Nursing (ILATGANA-PHN) to increase community capacity in natural disaster-prone areas.

Indonesia is at high risk of disasters. Therefore, nursing is expected to play a role in disaster risk reductions in communities. This study aimed to implement the Disaster Preparedness Training Integration Model based on Public Health Nursing (ILATGANA-PHN) to increase the Capacity of community in natural disaster-prone areas by assessing the preparedness level of families and communities in disaster-prone areas. The research method was developed in two stages, including the model preparation stage and the model implementation stage. This research was in the 2nd stage, namely the model impelementation stage. The research design, at the model implementation stage, used the one-sample pre-post test without control group design. The respondents were assessed before and after the ILATGANA-PHN training intervention. The sample size was calculated using the sample size calculation formula for the experimental research design without controls. The samples of the study were 78 people. The result of the research described the ILATGANA-PHN training concepts, including the instrument, curriculum, process, module, and maintenance patterns for the training process. The intervention had a significant effect on increasing the independent preparedness of the people in Kendeng Community, Sugih Mukti Village (Æ¿ 0.000 ≤ 0.005) in terms of four preparedness parameters, namely knowledge and attitudes about disasters (KA), disaster preparedness plans (PE), disaster warnings (WS), and resource mobilization community (RMC). Nurses have the opportunity to take responsibilities for empowering the community capacity in the disaster area through the implementation of ILATGANA-PHN training. The integrated training model for disaster preparedness based on Public Health Nursing (ILATGANA-PHN) is effective in increasing the community capacity, especially in disaster managements, in disaster-prone areas.

Metaproteomic and gene expression analysis of interspecies interactions in a PAH-degrading synthetic microbial consortium constructed with the key microbes of a natural consortium.

Polycyclic Aromatic Hydrocarbons (PAHs) impose adverse effects on the environment and human life. The use of synthetic microbial consortia is promising in bioremediation of contaminated sites with these pollutants. However, the design of consortia taking advantage of natural interactions has been poorly explored. In this study, a dual synthetic bacterial consortium (DSC_AB) was constructed with two key members (Sphingobium sp. AM and Burkholderia sp. Bk), of a natural PAH degrading consortium. DSC_AB showed significantly enhanced degradation of PAHs and toxic intermediary metabolites relative to the axenic cultures, indicating the existence of synergistic relationships. Metaproteomic and gene-expression analyses were applied to obtain a view of bacterial performance during phenanthrene removal. Overexpression of the Bk genes, naph, biph, tol and sal and the AM gene, ahdB, in DSC_AB relative to axenic cultures, demonstrated that both strains are actively participating in degradation, which gave evidence of cross-feeding. Several proteins related to stress response were under-expressed in DSC_AB relative to axenic cultures, indicating that the division of labour reduces cellular stress, increasing the efficiency of degradation. This is the one of the first works revealing bacterial relationships during PAH removal in a synthetic consortium applying an omics approach. Our findings could be used to develop criteria for evaluating the potential effectiveness of synthetic bacterial consortia in bioremediation.

Antioxidant and inflammatory biomarkers in herpes zoster.

The risk of herpes zoster (HZ) increases as cell-mediated immunity declines with age. Even though oxidative stress plays a crucial role in the development of HZ, there are few serum biomarkers of the disease's antioxidant activity. The purpose of this study is to investigate the blood levels of major antioxidants in HZ patients. To the best of our knowledge, this is the first study on this issue in the literature. The serum levels of antioxidants including uric acid (UA), total bilirubin (TBIL), albumin (ALB), vitamin D levels, and inflammatory markers such as homocysteine (Hcy) and C-reactive protein (CRP) was retrospectively analyzed in 53 patients with HZ and 53 age-and sex-matched healthy controls (HCs). The relationships between these markers and postherpetic neuralgia (PHN) and the clinical severity of HZ were also evaluated. Serum levels of UA, TBIL, and ALB in patients with HZ were significantly lower than those in the HCs (p < 0.001), while no statistical differences were found in vitamin D levels between the groups. Hcy and CRP levels were significantly increased in HZ patients compared to HCs. Significant differences were observed in the serum levels of UA, Hcy, CRP, and vitamin D in the PHN group versus the non-PHN group (p < 0.001). The presence of inflammatory markers was found to be positively related to disease activity. Furthermore, when compared to the mild or moderate clinical types of HZ, these biomarkers were statistically significant in the severe clinical type. These results suggest that uncontrolled varicella-zoster virus reactivation, acute nerve damage, and PHN may all be associated with low antioxidant levels. These biomarkers may be a protective factor for HZ, but more research is needed to clarify the underlying mechanism.

14-day famciclovir treatment significantly reduces the incidence of postherpetic neuralgia in elderly patients with herpes zoster.

WHAT IS KNOWN AND OBJECTIVE: Pain is the main symptom of herpes zoster (HZ), whilst postherpetic neuralgia (PHN) is a long-term unbearable pain, which seriously affects the quality of life of patients and is also the most intractable problem for clinicians. Early antiviral treatment is considered as a key measure to reduce acute pain and PHN. Nevertheless, most patients still have long-term pain after 7 days of antiviral treatment, and some patients will develop PHN. This study aimed to investigate whether prolonged duration of antiviral therapy could reduce HZ acute pain and the occurrence of PHN. METHODS: The outpatient data of HZ patients over 50 years old who visited the Dermatology Department from January 2016 to May 2018 were retrospectively analysed. According to the different courses of treatment of famciclovir (FCV), the patients were divided into 7-day FCV group and 14-day FCV group. The numerical rating scale (NRS) score at the first visit and on the 7th, 14th and 21st days after the start of treatment, the adverse drug reactions and the incidence of PHN were compared between the two groups. RESULTS: A total of 219 patients were involved in the analysis. For acute pain control, the 14-day FCV group was better than the 7-day FCV group. For patients with mild initial pain, there was no significant difference in NRS between the two treatments. For patients with moderate-to-severe initial pain, the NRS in the 14-day FCV group was significantly lower than that of the 7-day FCV group on the 14th and 21st days after starting treatment. PHN occurred in patients with moderate-to-severe initial pain, and the incidence was significantly lower in the 14-day FCV group than in the 7-day FCV group. There was no significant difference in the number of adverse reactions between the two groups. WHAT IS NEW AND CONCLUSION: Compared with the traditional 7-day antiviral therapy, the 14-day course of FCV can reduce the acute pain and the incidence of PHN in elderly patients with HZ, especially in patients with moderate to severe initial pain. Prolonging the course of medication did not increase the side effects.

Thermographic follow-up of postherpetic neuralgia (PHN) subsequent to Ramsay Hunt syndrome with multicranial nerve (V, VII, VIII and IX) involvement: a case report.

BACKGROUND: Ramsay Hunt syndrome (RHS) is caused by a reactivation of varicella-zoster virus (VZV) infection, and it is characterized by the symptoms of facial paralysis, otalgia, auricular rash, and/or an oral lesion. Elderly patients or immunocompromised patients, deep pain at the initial visit and no prompt treatment are significant predictors of postherpetic neuralgia (PHN). When PHN occurs, especially involved cranial polyneuropathy, multiple modalities should be administered for patients with the intractable PHN. The use of thermography in the follow-up of PHN secondary to RHS with multicranial nerve involvement has not yet been described yet in the literature. CASE PRESENTATION: The patient was a 78-year-old man with the chief complaint of a 3-month history of PHN secondary to RHS with polycranial nerve (V, VII, VIII, and IX) involvement. Multimodality therapy with oral gabapentin, pulsed radiofrequency (PRF) application to the Gasserian ganglion for pain in the trigeminal nerve region, linear-polarized near-infrared light irradiation for pain in the facial nerve region, and 2% lidocaine spray for pain in the glossopharyngeal nerve region was used to the treat patient, and follow-up evaluations included thermography. This comprehensive treatment obviously improved the quality of life, resulting in considerable pain relief, as indicated by a decrease in the numerical rating scale (NRS) score from 9 to 3 and a decrease in thermal imaging temperature from higher to average temperature on the ipsilateral side compared with the contralateral side. Lidocaine spray on the tonsillar branches of the glossopharyngeal nerve resulted in an improvement in odynophagia, and the NRS score decreased from 9 to 0 for glossopharyngeal neuralgia after three applications. CONCLUSION: Although the use of thermography in the follow-up of RHS with multiple cranial nerve (V, VII, VIII, and IX) involvement is very rare, in this patient, thermal imaging showed the efficacy of combination therapy (oral gabapentin, 2% lidocaine sprayed, PRF application and linear-polarized near-infrared light irradiation) and that is a good option for treatment.

Role of low-level laser therapy in post-herpetic neuralgia: a pilot study.

The aim of the present study was to investigate the influence of low-level laser radiation at a wavelength of 650 nm for treating post-herpetic neuralgia, an extremely painful condition which frequently occurs severely in old age and may persist for years with no predictable course. In total, fifteen patients were included in the present study, out of which 8 were females and 7 were males aged between 42 and 82 years. All patients were treated through 16 sessions for 8 weeks, and pain scoring was done on a visual analogue scale and statistical analysis was made for comparison before and after treatments. The final pain score was 0 in 11 patients although their initial pain score was severe in 8 and moderate in 3 patients. In three patients, pain reduced to mild intensity (2-3), and in one, the final pain score was 4 on the visual analogue scale. Patients treated during the present study have not complained for recurrence of pain or any other abnormality even after many months since completion of the therapy. Overall, low-level laser therapy (LLLT) proved itself an excellent therapeutic modality for the relief of pain in post-herpetic neuralgia patients, which may replace pain management medicines in future.

Phosphate uptake by the phosphonate transport system PhnCDE.

BACKGROUND: Phosphate is a fundamental nutrient for all creatures. It is thus not surprising that a single bacterium carries different transport systems for this molecule, each usually operating under different environmental conditions. The phosphonate transport system of E. coli K-12 is cryptic due to an 8 bp insertion in the phnE ORF. RESULTS: Here we report that an E. coli K-12 strain carrying the triple knockout ΔpitA Δpst Δugp reverted the phnE mutation when plated on complex medium containing phosphate as the main phosphorus source. It is also shown that PhnCDE takes up orthophosphate with transport kinetics compatible with that of the canonical transport system PitA and that Pi-uptake via PhnCDE is sufficient to enable bacterial growth. Ugp, a glycerol phosphate transporter, is unable to take up phosphate. CONCLUSIONS: The phosphonate transport system, which is normally cryptic in E. coli laboratory strains is activated upon selection in rich medium and takes up orthophosphate in the absence of the two canonical phosphate-uptake systems. Based on these findings, the PhnCDE system can be considered a genuine phosphate transport system.

The DNP/MPH Dual Degree: An Innovative Graduate Education Program for Advanced Public Health Nursing.

Strong professional priorities, evolving Affordable Care Act requirements, and a significantly limited public health nursing workforce prompted the University of Colorado College of Nursing to collaborate with the School of Public Health to implement one of the first Doctor of Nursing Practice/Master of Public Health dual degree programs in the nation. Federal grant funding supported the development, implementation, and evaluation of this unique post-baccalaureate dual degree program, for which there were no roadmaps, models, or best practices to follow. Several key issues emerged that serve as lessons learned in creating a new, novel higher education pathway for Advanced Public Health Nursing. This paper highlights two of those: (1) marketing, admission, and matriculation across two programs, and (2) enhancing curricula through distance coursework and interprofessional education. When collaboration with a school of public health is possible, the Doctor of Nursing Practice/Master of Public Health dual degree is an efficient way to prepare public health nurses' with the highest level of public health knowledge, practice, and leadership expertise.