Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial.

BACKGROUND: In a recent randomized, double-blind, placebo-controlled study, we observed a nonsignificant reduction of attack frequency in cluster headache after pulse administration of psilocybin (10 mg/70 kg, 3 doses, 5 days apart each). We carried out a blinded extension phase to consider the safety and efficacy of repeating the pulse regimen. METHODS: Eligible participants returned to receive a psilocybin pulse at least 6 months after their first round of study participation. Participants kept headache diaries starting two weeks before and continuing through eight weeks after the first drug session. Ten participants completed the extension phase and all ten were included in the final analysis. RESULTS: In the three weeks after the start of the pulse, cluster attack frequency was significantly reduced from baseline (18.4 [95% confidence interval 8.4 to 28.4] to 9.8 [4.3 to 15.2] attacks/week; p = 0.013, d' = 0.97). A reduction of approximately 50% was seen regardless of individual response to psilocybin in the first round. Psilocybin was well-tolerated without any unexpected or serious adverse events. DISCUSSION: This study shows a significant reduction in cluster attack frequency in a repeat round of pulse psilocybin administration and suggests that prior response may not predict the effect of repeated treatment. To gauge the full potential of psilocybin as a viable medicine in cluster headache, future work should investigate the safety and therapeutic efficacy in larger, more representative samples over a longer time period, including repeating the treatment. CLINICAL TRIALS REGISTRATION: NCT02981173.

Exploring Advancements in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review of Current Modalities and Future Prospects.

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable disease requiring a multidisciplinary treatment approach and a collaborative therapeutic effort. A combination of both upper and lower motor neuron degeneration ultimately leads to respiratory failure, similar to other dementia-type neurodegenerative diseases. The aim of this paper is to pioneer current ALS research by carrying out a narrative literature review of the current treatment modalities of the disease. Through these efforts, we hope to condense the most pertinent information regarding current treatments and enhance the management of ALS patients as a whole, giving these patients a better quality of life as the search for a cure continues. We used a Pubmed search strategy and specific MeSH terms for the selection of the literature articles using the keywords "ALS," "new treatment," "treatment," and "symptomatic treatment." A combination of pharmaceutical interventions, psychological support, and physical rehabilitation has been most effective in enhancing the quality of life of patients with ALS (PALS). Among potential pharmacological therapies, only a few have been approved by the US Food and Drug Administration(FDA) to be used to treat ALS and its symptoms. Other treatment modalities being considered include gene therapy, cellular therapy, psychological therapy, physical therapy, and speech therapy, alongside robotics, alternative feeding methods, and communication devices.

Investigations on artificially extending the spectral range of natural vision.

Organic semiconductors are being explored as retinal prosthetics with the prime attributes of bio-compatibility and conformability for seamless integration with the retina. These polymer-based artificial photoreceptor films are self-powered with light-induced signal strength sufficient to elicit neuronal firing events. The molecular aspect of these semiconductors provides wide spectral tunability. Here, we present results from a bulk heterostructure semiconductor blend with a wide spectral response range. This combination elicits clear spiking activity from a developing blind-chick embryonic retina in the subretinal configuration in response to white light. The response is largely triggered by the blue-green spectral regime rather than the red-NIR regime for the present polymer semiconductor layer attributes.

Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms.

BACKGROUND: Evidence suggests that serotonergic psychedelics (e.g. psilocybin), have rapid-acting and long-lasting antidepressant effects after a single dose. However, the mechanism underlying these effects remain unclear. One proposed mechanism is that these drugs promote neuroplasticity. However, this has not been conclusively demonstrated in humans. AIMS: We hypothesized that relative to placebo, psilocybin would: (1) increase electroencephalographic (EEG) correlates of neuroplasticity, (2) reduce depression symptoms, and (3) changes in EEG would correlate with improvements in depression. METHODS: In this double-blind, placebo-controlled, within-subject study, individuals with major depressive disorder (MDD; n = 19) were administered placebo followed by psilocybin (0.3 mg/kg) in a fixed order (placebo, followed by psilocybin 4 weeks later). EEG indices of neuroplasticity (tetanus-induced long-term potentiation) as assessed via auditory evoked theta (4-8 Hz) power and measures of depression (GRID Hamilton Rating Scale for Depression-17 (GRID-HAM-D-17)) were measured at several time-points after placebo and psilocybin (24 h and 2 weeks after each session). RESULTS: EEG theta power doubled in amplitude 2 weeks after a single psychedelic dose of psilocybin but not after placebo. Further, improvements in depression symptoms 2 weeks after psilocybin were correlated with increases in theta power. CONCLUSIONS: The increased theta power observed represents evidence of sustained changes in the brain following psilocybin. Given the correlation with enhancement in depressive symptoms, changes in theta may represent an EEG biomarker of the sustained effects of psilocybin, and may shed light on potential mechanisms of psilocybin's antidepressant effect. Taken together, these results complement the emerging notion that psilocybin, and perhaps other psychedelics, can produce long-term alterations in neuroplasticity.

Ethylene Diamine Tetra Acetate-Induced Pseudo Thrombocytopenia (EDTA-PTCP) in an Adolescent: A Case Report.

Ethylene diamine tetra acetate-induced pseudo thrombocytopenia (EDTA-PTCP) is a fictitious laboratory condition that is associated with platelet clumping, leading to falsely low platelet counts. This fictitious occurrence can lead to expensive, time-consuming, and invasive diagnostic procedures. It may also result in the application of unnecessary therapies, although it is not linked to any hemorrhagic symptoms or platelet malfunction. This emphasizes the necessity of verifying laboratory results from automated analyzers in every patient with thrombocytopenia with a peripheral smear, particularly when they are out of proportion when compared to the clinical features. When using hematology analyzers, EDTA-induced pseudo thrombocytopenia can be missed. In cases of isolated thrombocytopenia, this can be easily avoided by performing a simple visual peripheral blood smear check, hence making it an important differential for thrombocytopenia on an automatic analyzer report, which has to be ruled out. Here, we present the case of an adolescent who presented to us with low platelet counts and was diagnosed with EDTA-PTCP after proper evaluation.

Neuroendocrine Carcinoma of Cervix: A Case Series.

Cervical cancer is the second most common cause of cancer-related mortality in women globally. Neuroendocrine carcinomas are among the rarest and least studied histopathological types of cervical cancers, accounting for 1.4% of all cervical cancers. Neuroendocrine carcinomas of the cervix (NECCs) are aggressive tumors that can be associated with several high-risk features such as early lymphovascular invasion and multiple systemic metastases, at early stages. Here, we present a case series of five patients with NECC who have been diagnosed and managed at a tertiary care hospital in coastal Andhra Pradesh, South India. Using the hospital records, we made a list of patients with NECC who were diagnosed by histopathological findings between 2019 and 2022. Details regarding their demographic variables, presenting complaints, staging, and treatment given were noted down using a pre-defined proforma.

Effect of ER, CR: YSGG laser debonding on enamel surface changes in stainless steel and ceramic brackets - An in-vitro study.

AIM: The aim of this in-vitro study was to observe and analyze the various enamel surface changes that occur due to laser debonding of metal and ceramic brackets, done by means of Er, Cr:YSGG laser. MATERIALS AND METHODS: 90 extracted premolars were randomly allocated into one of six groups with 15 teeth each. The groups represent metal brackets (Groups A1, A2, A3) and ceramic brackets (Groups B1, B2, B3). Each sub-group represents the mode of debonding used in the study. Debonded teeth were analyzed under scanning electron microscopy (SEM) at 80X and at 1000X magnification at three sites. The adhesive remnant index (ARI) scores were analyzed and the presence of enamel damage was observed. RESULT: ARI showed high score in Groups A1 and B1. SEM images of large composite remnants at the site of bracket in Groups A1 and B1 at the site of bracket and multiple enamel microcracks and fractures at interface and enamel adjacent to bracket in Groups A1 and B1. SEM images of minimal composite remnants at the site of bracket in Groups A2, A3, B2, and B3 and little to no presence of enamel microcracks or fractures at interface and enamel adjacent to bracket in Groups A2, A3, B2, and B3. CONCLUSION: The use of Er, Cr:YSGG laser in orthodontic practice, especially in the debonding procedures of orthodontic brackets provide quality care to patient with minimal post-treatment damages.

Evaluation of psychometric properties of a leaflet developed for schizophrenia.

BACKGROUND: Patients with severe mental illnesses like schizophrenia may benefit from a variety of patient education materials. Despite the availability of various resources, it is essential to assess the extent to which patients can comprehend the materials provided. OBJECTIVE: This study aims to evaluate the reliability and readability of the patient information leaflet (PIL) for schizophrenia. METHOD: A quasi-experimental study was conducted for a period of 6 months in the departments of psychiatry. Patients with a diagnosis of schizophrenia were recruited for the study. A user-testing questionnaire was developed and validated with the help of an expert committee to assess reliability. Later, translated versions of the questionnaire were then administered to the patients based on their language preference and evaluated by test-retest analysis. The readability was assessed using pre-validated and translated versions of the PIL. Initially, baseline scores of patient knowledge were assessed using a reliable user-testing questionnaire. Later, their responses were reassessed again using the same questionnaire after reading the PIL. RESULTS: A total of 45 patients participated in the study. From the total sample, 20 participants were randomly selected for reliability assessment. Intraclass-correlation coefficient (ICC), a statistical tool of reliability, give .6 for Kannada, .7 for Malayalam and 1 for the English version of the questionnaire. The overall patient's knowledge was found to be improved from 50.4 to 76.4 after reading the PIL. CONCLUSION: Patients with schizophrenia were able to comprehend the information available on the PIL. Therefore, further research is needed to determine its efficacy in a larger population.

Intralesional Steroid Injection Versus Extracorporeal Shockwave Therapy in the Treatment of Plantar Fasciitis: A Comparative, Prospective, Case Series Study.

Background This study aimed to compare and evaluate the outcomes of intralesional steroid injections (ultrasound-guided) versus extracorporeal shockwave therapy in the treatment of plantar fasciitis. Methodology Between January 2021 and March 2022, 120 (84 male, 36 female) patients with a confirmed diagnosis of plantar fasciitis were identified. Subjective assessment was done using Mayo Clinical Score, and objective evaluation was done by measuring plantar fascia thickness using ultrasonography. For this study, two groups were made, wherein group A was administered a high dose of extracorporeal shockwave therapy, and group B was administered ultrasound-guided intralesional or local steroid injections. Results Plantar fascia thickness was considerably reduced after therapy in both groups; however, the difference in thickness reduction was not statistically significant between both groups. Mayo Clinic Scores showed statistically significant improvement in pain; however, the difference in pain reduction was not statistically significant between both groups. Conclusions A considerable clinical and radiological improvement was noted in both groups; however, we did not record statistically significant and superior results in either group. Intralesional steroid injections provided faster clinical improvement and better patient compliance.

COVID-19 vaccination up-take in three districts of Nepal.

Vaccine hesitancy during the COVID-19 pandemic continues to be an issue in terms of global efforts to decrease transmission rates. Despite high demand for the vaccines in Nepal, the country still contends with challenges related to vaccine accessibility, equitable vaccine distribution, and vaccine hesitancy. Study objectives were to identify: 1) up-take and intention for use of COVID-19 vaccines, 2) factors associated with vaccine up-take, and 3) trusted communication strategies about COVID-19 and the vaccines. A quantitative survey was implemented in August and September 2021 through an initiative at the Nepali Ministry of Health and Population Department of Health Services, Family Welfare Division. Data were collected from 865 respondents in three provinces (Bagmati, Lumbini, and Province 1). Ordinal multivariate logistic regression was utilized to determine relationships between vaccination status and associated factors. Overall, 62% (537) respondents were fully vaccinated and 18% (159) were partially vaccinated. Those respondents with higher education (p < .001) and higher household income (p < .001) were more likely vaccinated. There were also significant differences in vaccine up-take across the three provinces (p < .001). Respondents who were vaccinated were significantly more likely to perceive vaccines as efficacious in terms of preventing COVID-19 (p = .004) and preventing serious outcomes (p = .010). Among both vaccinated and unvaccinated individuals, there was a high level of trust in information about COVID-19 vaccines provided through local health-care workers [e.g. nurses and physicians]. These results are consistent with other findings within the South Asia region. Targeted advocacy and outreach efforts are needed to support ongoing COVID-19 vaccination campaigns throughout Nepal.

Delta-9-Tetrahydrocannabinol, Cannabidiol, and Acute Psychotomimetic States: A Balancing Act of the Principal Phyto-Cannabinoids on Human Brain and Behavior.

Background: THC and CBD are the principal phyto-cannabinoids in the cannabis plant. The differential and possibly antagonistic effects of these compounds on specific brain and behavioral responses, and the mechanisms underlying their effects have generated extensive interest in pre-clinical and clinical neuroscience investigations. Methods: In this double-blind randomized placebo-controlled counterbalanced Human Laboratory Study, we examined the effects of three different dose ratios of CBD:THC (1:1, 2:1, and 3:1) on "neural noise," an electrophysiological biomarker of psychosis known to be sensitive to cannabinoids as well as subjective and psychotomimetic effects. Healthy volunteers (n=28, 12 women) with at least one prior exposure to cannabis participated in the study. Outcomes: The lowest CBD (2.5 mg):THC (0.035 mg/kg) ratio (1:1) resulted in maximal attenuation of both THC-induced psychotomimetic effects (Positive and Negative Syndrome Scale [PANSS] positive: Anova Type Statistic [ATS]=7.83, pcorrected=0.015) and neural noise (ATS=8.83, pcorrected=0.009). Further addition of CBD did not reduce the subjective experience of THC-induced "high" (p>0.05 for all CBD doses). Interpretation: These novel results demonstrate that CBD attenuates specific THC-induced subjective and objective effects relevant to psychosis in a dose/ratio-dependent manner. Given the increasing global trend of cannabis liberalization and application for medical indications, these results assume considerable significance given the potential dose-related interactions of these key phyto-cannabinoids. Trial registration: The trial was registered in clinicaltrials.gov ID: NCT01180374.

The Outcome of Placing the Medial K-wire First and Then the Lateral K-wire in Treating Supracondylar Humerus Fractures in Children Treated by Closed Reduction.

Background Displaced Gartland type III and IV supracondylar fractures are difficult to reduce and invariably require closed pining. After closed reduction, taking the anteroposterior (AP) view does not present any problem but when the elbow is placed in flexion and the limb is rotated internally to take a lateral view, the reduction is invariably lost. However, the reduction stays when the arm is rotated outwards, keeping the medial condyle up. This stimulates the idea of whether the medial pin can be placed first and then the two lateral pins to stabilize the fracture. It is very frustrating for young orthopedic surgeons to see reduction getting lost during internal rotation after first doing lateral pinning. There is no clear guideline on which side should be fixed first. Hypothesis We hypothesized that placing the medial pin first maintains the reduction and facilitates the subsequent placing of lateral pins without the loss of reduction. Materials and methods A total of 170 children with displaced supracondylar humerus fractures were included in the study. A total of 120 children were grouped in the medial wire first group, and 50 were placed in the lateral wire first group, which was the control group. The mean age of the children was 7.5 years (range 2-13 years). The gender ratio (M: F) was 5:3; the left elbow was involved in 68% of the injuries, whereas the right elbow was involved in 32% of the injuries. All 170 children had an extension-type injury, with 91 (53.5%) fractures being Gartland type III and 79 (46.45%) fractures being type IV. Results Results were recorded as per Flynn's criteria. At the end of two years of follow-up, the children in the medial wire first group 117 (97.5%) showed excellent results and three (2.5%) children showed good results, whereas, in the lateral wire first group, 48 (96%) children showed excellent results and two (3.8%) children showed good results. There was a significant difference in the mean surgical time of 20.11±15.43 minutes in the medial wire first group vs 41.23±19.65 minutes in the lateral first group (p = 0.0021). None of the children developed permanent ulnar nerve palsy. Conclusions Placing the medial K-wire first rather than the conventional placing of the lateral wire first helps in maintaining the reduction and allows for the subsequent placement of lateral K-wires without losing the reduction, thus minimizing fixation time and producing good results.

Exploratory investigation of a patient-informed low-dose psilocybin pulse regimen in the suppression of cluster headache: Results from a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Using a patient-informed regimen, we conducted an exploratory randomized, double-blind, placebo-controlled study to systematically investigate the effects of psilocybin in cluster headache. BACKGROUND: Sustained reductions in cluster headache burden after limited quantities of psilocybin-containing mushrooms are anecdotally reported, although to date there are no controlled studies investigating these effects. METHODS: Participants were randomized to receive psilocybin (0.143 mg/kg) or placebo (microcrystalline cellulose) in a pulse of three doses, each ~5 days apart. Participants maintained headache diaries starting 2 weeks before and continuing through 8 weeks after the first drug session. A total of 16 participants were randomized to receive experimental drug and 14 were included in the final analysis. RESULTS: In the 3 weeks after the start of the pulse regimen, the change in cluster attack frequency was 0.03 (95% confidence interval [CI] -2.6 to 2.6) attacks/week with placebo (baseline 8.9 [95% CI 3.8 to 14.0]) and -3.2 (95% CI -8.3 to 1.9) attacks/week with psilocybin (baseline 9.6 [95% CI 5.6 to 13.6]; p = 0.251). Group difference in change from baseline had a moderate effect size (d = 0.69). The effect size was small in episodic participants (d = 0.35) but large in chronic participants (d = 1.25), which remained over the entire 8-week period measured (d = 0.81). Changes in cluster attack frequency were not correlated with the intensity of acute psychotropic effects during psilocybin administration. Psilocybin was well-tolerated without any unexpected or serious adverse events. CONCLUSIONS: Findings from this initial, exploratory study provide valuable information for the development of larger, more definitive studies. Efficacy outcomes were negative, owing in part to the small number of participants. The separation of acute psychotropic effects and lasting therapeutic effects underscores the need for further investigation into the mechanism(s) of action of psilocybin in headache disorders.

Intraoperative Use of Ultrasonography in the Reduction of Zygomatico-Maxillary Complex Fractures.

Study Design: A single blind randomized controlled study. Objective: The aim of this study is to evaluate the use of ultrasonography intraoperatively to assess the reduction of unilateral zygomatic complex fractures with a control group using the conventional blind digit palpation. Methods: The study comprised of a sample size of 24 patients with 21 male and 3 female patients. Patients of all age groups diagnosed with unilateral displaced zygomatic complex fracture with or without mandible fracture were included in the study. The subjects were randomized into study and control groups based on a standard protocol with a total of 24 patients. Imaging was in the form of a preoperative and postoperative 3D computed tomography scan with reconstruction of the maxilla and mandible to interpret the diagnosis for all subjects. The inter-fracture distance of the fractured infraorbital rim were measured in 3 dimensions (antero-posterior, medio-lateral and supero-inferior) and compared pre and postoperatively. Preoperative, intraoperative and postoperative ultrasonographic examination was performed and recorded on all patients at the frontozygomatic region, infraorbital rim and zygomatic buttress to assess the proximity of the fractured margins pre reduction, post reduction and post fixation of the fracture segments. Result: Statistical analytic results were significant in all 3 dimensions when measured postoperatively using computed tomography. Conclusion: Ultrasonography is an effective screening and intraoperative tool in the armamentarium of oral and maxillofacial surgery to assess zygomatic complex fractures, avoiding incisions in aesthetic areas of the maxillofacial region.

Analysis of circulating exosomes reveals a peripheral signature of astrocytic pathology in schizophrenia.

OBJECTIVES: Extracellular vesicles, including exosomes, cross the blood brain barrier with their contents intact and can be assayed peripherally. Circulating exosomes have been studied in other neurodegenerative disorders, but there is scarce data in schizophrenia. This study aimed to examine neuropathology-relevant protein biomarkers in circulating plasma-derived exosomes from patients with schizophrenia and age- and sex-matched healthy controls. METHODS: Nanoparticle tracking analysis was used to determine the size and concentration of exosomes. Exosomal membrane marker (CD9) and specific target cargo protein (glial fibrillary acid protein[GFAP], synaptophysin, and α-II-Spectrin) immunopositivity was examined using Western blot analyses with band intensity quantified. Methods were consistent with the 'Minimal information for studies of extracellular vesicles 2018' (MISEV2018) guidelines. RESULTS: Exosomal GFAP concentration was significantly higher and α-II-Spectrin expression significantly lower in plasma obtained from schizophrenia patients. No group differences were observed between in plasma exosomal concentration and size or in CD9, calnexin, or synaptophysin levels. CONCLUSIONS: Our results demonstrate a differential pattern of exosomal protein expression in schizophrenia compared to matched healthy controls, consistent with the hypothesised astroglial pathology in this disorder. These results warrant further examination of circulating exosomes as vehicles of novel peripheral biomarkers of disease in schizophrenia and other neuropsychiatric disorders.

In vivo evidence of lower synaptic vesicle density in schizophrenia.

Decreased synaptic spine density has been the most consistently reported postmortem finding in schizophrenia (SCZ). A recently developed in vivo measure of synaptic vesicle density estimated using the novel positron emission tomography (PET) ligand [11C]UCB-J is a proxy measure of synaptic density. In this study we determined whether [11C]UCB-J binding, an in vivo measure of synaptic vesicle density, is altered in SCZ. SCZ patients (n = 13, 3 F) and age-, gender-matched healthy controls (HCs) (n = 15, 3 F) underwent PET imaging using [11C]UCB-J and high-resolution research tomography (HRRT). [11C]UCB-J distribution volume (VT) and binding potential (BPND) were estimated using a 1T model with centrum-semiovale as the reference region. Relative to HCs, SCZ patients, showed significantly lower [11C]UCB-J BPND with significant differences in the frontal cortex (-10%, Cohen's d = 1.01), anterior cingulate (-11%, Cohen's d = 1.24), hippocampus (-15%, Cohen's d = 1.29), occipital cortex (-14%, Cohen's d = 1.34), parietal cortex (-10%, p = 0.03, Cohen's d = 0.85) and temporal cortex (-11%, Cohen's d = 1.23). These differences remained significant after partial volume correction. [11C]UCB-J BPND did not correlate with cumulative antipsychotic exposure or gray-matter volume. Consistent with the postmortem and in vivo findings, synaptic vesicle density is lower across several brain regions in SCZ. Frontal synaptic vesicle density correlated with psychosis symptom severity and cognitive performance on social cognition and processing speed. These findings indicate that [11C]UCB-J PET is a sensitive tool to detect lower synaptic density in SCZ and holds promise for future studies of early detection and disease progression.

New record of Megalestes gyalsey Gyeltshen, Kalkman amp; Orr, 2017 (Zygoptera: Synlestidae) from India, with first description of female and larva.

Megalestes gyalsey Gyeltshen, Kalkman Orr, 2017 is recorded for the first time from India, extending the known geographic range of the species. This report is based on the collection of 5 individuals (4 males, 1 female) from Jang waterfall, Tawang, Arunachal Pradesh and 2 males from Neora Valley National Park, Kalimpong district, West Bengal. The female of M. gyalsey is described for the first time with notes on the variation in the male. A probable larva of the species is also described and illustrated.