Cervical manipulation and associated cardiovascular risks

openScopo dello studio La presenza di una correlazione tra la manipolazione cervicale HVLA (High Velocity Low Amplitude) e un avvenimento cardiovascolare avverso rimane ancora oggi senza una risposta chiara. Coloro che utilizzano la manipolazione (chiropratici, osteopati and fisioterapisti), certi della sicurezza visti i bassi rapporti di probabilità con cui può avvenire un evento avverso, affermano che non sussistono problematiche e talvolta non informano il paziente dei rischi. I medici, soprattutto neurologici, rimarcano che le complicanze creino quadri patologici gravi seppur siano rare sconsigliando l’utilizzo della manipolazione. Questa revisione della letteratura si pone come obiettivo di trovare la risposta al quesito per cui la manipolazione sia la causa degli eventi avversi cardiovascolari. Materiali e metodi La ricerca è stata eseguita su PubMed da Luglio ad Agosto 2023 includendo gli studi e le revisioni in ogni lingua che contenessero l’analisi della correlazione tra la manipolazione e gli eventi cardiovascolari avversi. Sono stati esclusi gli studi su cadaveri, case report, case series, sondaggi, commenti Risultati e Discussione Le revisioni della letteratura hanno riscontrato la presenza della correlazione basandosi però sugli stessi studi caso-controllo e sulla grande presenza in letteratura di case report e case series. Gli studi riportano, invece, la possibilità che la manipolazione sia solo uno dei fattori meccanici scatenanti e come possa essere la compresenza di più fattori la causa dell’evento avverso cardiovascolare. Inoltre, in altri studi viene evidenziato come, data la sintomatologia tipica dell’evento avverso, mal di testa e dolore al collo, il paziente si rechi sia dal medico che dal terapista manuale. Essendo l’associazione risultata statisticamente significativa sia per quanto riguarda la terapia manipolatoria che per le visite dal medico di base, in alcuni studi viene riportato come non sia possibile scartare l’ipotesi nulla (in nessun caso è presente la correlazione). Conclusione Seppur non ci sia ancora una risposta certa, gli ultimi studi emersi, i quali sono successivi alle revisioni trovate, hanno riportato tutti l’assenza della correlazione, riaprendo la questione. È chiaro come, nonostante sia complesso per la rarità della problematica, portare uno studio prospettico con un maggior numero di soggetti sia necessario. Allo stesso modo data la sporadicità degli eventi, rimane importante e fondamentale eseguire al meglio lo screening del paziente così da riconoscere le “red flags”, quali il dolore al collo, il mal di testa e altri traumi al collo subiti in precedenza che possono richiamare la problematica di un evento cardiovascolare avverso in corso.Purpose of the study To today the presence of an association between cervical manipulation HVLA (High Velocity Low Amplitude) and an adverse cardiovascular event is still without a certain answer. Those practioner who use manipulation (chiropractors, osteopath and physio/physical therapist), confident in its safety from the low probability with which an adverse event can occur, claim that there are no problems and sometimes they do not inform the patient of the risks. Doctors, especially neurologist, point out that these complications create serious pathological scenario although they are rare advising to not use the manipulation. This review of the literature aims to find the answer to the question of whether manipulation is the cause of adverse cardiovascular events. Methods The search was performed on PubMed from July to August 2023 including studies and reviews in each language that contained the analysis of the association between the manipulation and adverse events. Studies on cadavers, case reports, case series, surveys and comments were excluded. Results and discussion The reviews have found the presence of a correlation, however, it was based on the same case-control studies and on the large presence of case reports and case series in the literature. Instead, the studies report the possibility that the manipulation is actually one of the mechanical trigger factors and that the co-presence of multiple ones could be the cause of the adverse cardiovascular event. Nevertheless, in some studies it is highlighted how, given the typical symptoms of the adverse event, headache and neck pain, the patient seeks help to the doctor and manual therapist. Since the association was found stastically significant for both the primary care doctor and manual therapist, some articles suggest the null hypothesis (in both cases there is no correlation). Conclusion Although there is not yet a certain answer, the latest studies, which follow all the reviews found, have all reported the absence of an association, reopening the question. Despite being complex due to the rarity of the problem, carrying out a prospective study with a greater number of subjects is necessary. Likewise, given the sporadic nature of the events, it remains important and fundamental to perform the best screening of the patient to recognize the "red flags", such as neck pain, headaches and other neck traumas suffered previously by the patients, which may recall an ongoing adverse cardiovascular event

Pathogenicity markers of Clostridium spp. in commercial turkeys

Since growth promoters ban in Europe, enteritis of different aetiologies (virus, bacteria and protozoa) are increasingly becoming the main cause of economic loss in commercial turkeys production. This study is focused on typing of Clostridium spp. isolated from samples of jejunum and ileum of 82 birds out of 17 turkeys flocks. The birds were 6-day to 104-day old, both male and female, with enteric disorders. The presence of toxin NetB was investigated. Multiplex PCR to detect cpa, cpb1, cpetx, cp1, cpb2 and cpe toxin genes were used for Clostridium typing. No lesions of necrotic enteritis were observed. Clostridium perfringens type A was isolated from 25 enteric samples, Clostridium difficile was found in 4 cases and Clostridium sordelli in one case. Clostridium perfringens was present from 6 to 104 days of age indicating its possible role in the enteric disorders of commercial turkeys. NetB toxin was found in no sample. 3 out of 4 isolates of Clostridium difficile were characterized by the presence of toxin genes

Accelerating the Development and Transfer of Freeze-Drying Operations for the Manufacturing of Biopharmaceuticals by Model-Based Design of Experiments

In the pharmaceutical industry, freeze-drying (also known as lyophilization) is often used to increase the shelf life of heat-sensitive biopharmaceuticals such as protein-based therapeutic drugs an..

Primary Drying Optimization in Pharmaceutical Freeze-Drying: A Multivial Stochastic Modeling Framework

Primary drying is the most time-consuming and energy-intensive step in pharmaceutical freeze-drying. Minimizing the duration of this stage is of paramount importance to speed up process development..

Closing Clostridium botulinum Group III Genomes Using Long-Read Sequencing

Clostridium botulinum group III is the anaerobic Gram-positive bacterium producing the deadly neurotoxin responsible for animal botulism. Here, we used long-read sequencing to produce four complete genomes from Clostridium botulinum group III neurotoxin types C, D, C/D, and D/C. The protocol for obtaining high-molecular-weight DNA from C. botulinum group III is described.Peer reviewe

The first non Clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain

The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified Weissella metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo

Rapid kidney function decline and increased risk of heart failure in patients with type 2 diabetes: findings from the ACCORD cohort : Rapid kidney function decline and heart failure in T2D.

BACKGROUND Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors. METHODS Included in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period (median eGFR/year = 1.9, IQR 1.7-3.2). The association between rapid kidney function decline (eGFR loss ≥ 5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI). RESULTS Over 4 years of follow-up, 1,573 participants (20.9%) experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds (3.23, 95% CI, 2.51-4.16, p < 0.0001), independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring (3.74; 95% CI 2.63-5.31). Adding rapid kidney function decline during follow-up to other clinical predictors (WATCH-DM score, eGFR, and UACR at study entry and end of follow-up) improved HF risk classification (ROC AUC = + 0.02, p = 0.027; relative IDI = + 38%, p < 0.0001). CONCLUSIONS In patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D

Genome Sequence of the Fish Brain Bacterium Clostridium tarantellae

Eubacterium tarantellae was originally cultivated from the brain of fish affected by twirling movements. Here, we present the draft genome sequence of E. tarantellae DSM 3997, which consists of 3,982,316\u2009bp. Most protein-coding genes in this strain are similar to genes of Clostridium bacteria, supporting the renaming of E. tarantellae as Clostridium tarantella

Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.Peer reviewe