Highly (regio)selective hydroformylation of olefins using self-assembling phosphines.

New phosphines with self-assembling 6-pyridinone moities were prepared, characterized, and examined in the hydroformylation of diverse olefins. Testing various known and novel ligands in the presence of [Rh(acac)(CO)2] under industrially relevant conditions, the hydroformylation of 1-octene proceeds best with 6,6'-(phenylphosphanediyl)bis(pyridin-2(1H)-one) (DPONP). Control experiments and modelling studies indicate dimerization of this ligand at higher temperatures (>100 °C). The optimal catalyst system is able to conserve high product linearity (>90%) for a broad range of olefins at industrially-employed temperatures at low ligand loading.

Stability of class II correction with the Austro Repositioner associated with multi-brackets fixed appliances in dolichofacial patients.

BACKGROUND: The purposes of the present study were to evaluate the changes produced by the Austro Repositioner, and to assess the stability of Class II malocclusion treatment with the Austro Repositioner associated with fixed appliances and its capacity to control the vertical dimension in dolichofacial patients. METHODS: A group of patients with Class II malocclusion due to mandibular retrognathism and a dolichofacial growth pattern treated with the Austro Repositioner combined with fixed appliances were compared to a matched untreated control group of subjects with Class II malocclusion. Evaluations were made on the basis of lateral cephalograms taken at T1 (initial records), T2 (end of treatment), and T3 (1 year after treatment). Statistical comparisons were performed with paired- and two-sample t tests. RESULTS: The experimental (treated) group comprised 30 patients, 14 boys and 16 girls, and the control group comprised 30 subjects (15 boys and 15 girls) with similar ages at T1, T2 and T3. In the treated group, a significant decrease in the ANB angle was found (- 3.79 ± 1.46; p < 0.001). No significant differences were found in the maxillary skeletal measurements. In contrast, the SNB angle showed a significant increase of 3.77 ± 1.49 in the treated group compared with a nonsignificant increase of 0.77 ± 1.55 in the control group (p = 0.002). Vertical changes showed a significant decrease in the FMA angle (- 3.36 ± 1.62), while the lower anterior facial height distance and the overbite increased significantly in the treated group, reflecting a change in vertical dimensions after treatment. No significant changes were observed in either the treated or control group during the one-year posttreatment period; thus, the treatment results remained stable. CONCLUSIONS: The Austro Repositioner combined with fixed appliances could be considered an optimal treatment modality in Class II dolichofacial patients.

A Secretory Vesicle Failure in Parkinson's Disease Occurs in Human Platelets.

OBJECTIVE: The presence of elevated dopamine (DA) and its major metabolites in the cytosol of neurons has been associated with their vulnerability in Parkinson's disease (PD). Over 99% of the cell's amines are confined to secretory vesicles (SVs), making these structures fundamental in the regulation of cytosolic DA levels. SVs of platelets use similar, if not the same mechanisms to accumulate serotonin in SVs as dopaminergic neurons do to store DA. Hence, any functional defects in platelets probably mirrors events in DA neurons. METHODS: We have isolated fresh platelets from the blood of 75 PD patients, 116 matched controls and 24 patients with Parkinsonism, assaying serotonin handling (basal content, accumulation, secretion and spontaneous leakage). RESULTS: We found a dramatic decrease in the serotonin content and uptake by SVs, as well as decreased thrombin-induced release by platelets from PD patients but not in those from most Parkinsonism cases. Platelets from PD patients also failed to retain serotonin in SVs. INTERPRETATION: These findings indicate a functional impairment in the handling of amines by SVs in PD patients. This defect may serve as a biomarker of PD, and the approach described here may be potentially used for the subclinical detection of PD and to establish a platform to assay disease modifying drugs. ANN NEUROL 2022.

Effectiveness and safety profile of greater occipital nerve blockade in cluster headache: a systematic review.

BACKGROUND: Greater occipital nerve (GON) blockade is a short-term preventive therapy for cluster headache (CH). We conducted a systematic review to evaluate the effectiveness and safety of GON blockade in patients with CH. METHODS: On 23 October 2020, we searched MEDLINE, Embase, Embase Classic, PsycINFO, CINAHL, CENTRAL and Web of Science databases from their inception date. Studies included participants with a CH diagnosis who received corticosteroid and local anaesthetic suboccipital region injections. Outcomes were change in the frequency/severity/duration of attacks; proportion of participants responding to treatment, time to attack freedom from an attack, change in attack bout length and/or the presence of adverse effects after GON blockade. Risk of bias was assessed with the Cochrane Risk of Bias V.2.0 (RoB2)/Risk of Bias in Non-randomized Studies - of Interventions (ROBINS- I) tools and a specific tool for case reports/series. RESULTS: Two RCTs, eight prospective and eight retrospective studies, and four case reports were included in the narrative synthesis. Every effectiveness study found a significant response in one or more of frequency/severity/duration of individual attacks or proportion of patients responding to treatment (47.8%-100.0%). There were five instances of potentially irreversible adverse effects. A higher injectate volume and use of concurrent prophylaxis may be associated with an increased likelihood of response. Methylprednisolone may have the best safety profile of available corticosteroids. DISCUSSION: GON blockade is safe and effective for CH prevention. Higher injectate volumes may improve likelihood of response, and the likelihood of serious adverse events may be reduced by using methylprednisolone. PROSPERO REGISTRATION NUMBER: CRD42020208435.

Erenumab in chronic migraine: Experience from a UK tertiary centre and comparison with other real-world evidence.

BACKGROUND AND PURPOSE: Chronic migraine is a highly disabling primary headache disorder that is the most common diagnosis of patients seen at tertiary headache centres. Typical oral preventive therapies are associated with many limitations that impact their therapeutic utility. Erenumab was the first available calcitonin gene-related peptide monoclonal antibody in the UK. It had proven efficacy in migraine prevention in clinical trials and limited real-world data in tertiary settings. METHODS: We audited our first 92 patients (n = 73 females) with severely disabling chronic migraine who were given monthly erenumab 70 mg sc for 6 months between December 2018 and December 2019. RESULTS: At 3 months, monthly migraine days were significantly reduced by a median of 4 days, and all other variables also showed significant improvement. The improvement was not affected by baseline analgesic use status. More than half of our patients experienced a clinically meaningful improvement in migraine days. No serious adverse events were reported. CONCLUSIONS: Our real-world data with erenumab demonstrate it is effective and well tolerated in managing patients with chronic migraine in a tertiary care setting.

Targets for migraine treatment: beyond calcitonin gene-related peptide.

PURPOSE OF REVIEW: Despite the development of several medications for the acute and preventive treatment of migraine, there are still many patients in whom lack of efficacy, tolerability, interactions or contraindications make other options necessary. CGRP-based drugs have opened the door to a new era of migraine-targeted treatments. Beyond CGRP, there are other promising targets covered here. RECENT FINDINGS: For the acute treatment of migraine, 5-HT1F receptor agonists, ditans, are now available. Unlike triptans, 5-HT1B/1D receptor agonists, cardiovascular disease is not a contraindication for the use of ditans. The first study on a monoclonal antibody targeting PAC1 receptor was negative, although this may not be the end for the pituitary adenylate cyclase-activating polypeptide (PACAP) pathway as a target. SUMMARY: Following positive phase-III clinical trials, lasmiditan is the first ditan to be FDA-approved. PACAP has experimental evidence suggesting a role in migraine pathophysiology. As for CGRP, the presence of PACAP in key migraine structures along with positive provocative tests for both PACAP-38 and PACAP-27 indicate this pathway may still be a pharmacological target. Glutamate-based targets have long been considered in migraine. Two clinical trials with memantine, an NMDA-R antagonist, for the preventive treatment of migraine have now been published. The hypothalamus has also been implicated in migraine pathophysiology: the potential role of orexins in migraine is discussed. Acid-sensing ion channels, as well as amylin-blocking drugs, may also become migraine treatments in the future: more research is warranted.

Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland-Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from -0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the 'ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there is insufficient evidence for robust and reproducible sTILs-guided therapeutic decisions.

Indomethacin-responsive headaches-A narrative review.

BACKGROUND: Indomethacin is a nonsteroidal anti-inflammatory drug whose mechanism of action in certain types of headache disorders remains unknown. The so-called indomethacin-responsive headache disorders consist of a group of conditions with a very different presentation that have a particularly good response to indomethacin. The response is so distinct as to be used in the definition of two: hemicrania continua and paroxysmal hemicrania. METHODS: This is a narrative literature review. PubMed and the Cochrane databases were used for the literature search. RESULTS: We review the main pharmacokinetic and pharmacodynamics properties of indomethacin useful for daily practice. The proposed mechanisms of action of indomethacin in the responsive headache disorders, including its effect on cerebral blood flow and intracranial pressure, with special attention to nitrergic mechanisms, are covered. The current evidence for its use in primary headache disorders, such as some trigeminal autonomic cephalalgias, cough, hypnic, exertional or sexual headache, and migraine will be covered, as well as its indication for secondary headaches, such as those of posttraumatic origin. CONCLUSION: Increasing understanding of the mechanism(s) of action of indomethacin will enhance our understanding of the complex pathophysiology that might be shared by indomethacin-sensitive headache disorders.

Association between prenatal exposure to air pollutants and newborn thyroxine (T4) levels.

BACKGROUND: Thyroid hormones play a key role in fetal and child development. Recent studies have linked prenatal exposure to atmospheric contaminants with changes in thyroid hormone levels in newborns, but the data from the few studies that have explored this issue are inconclusive. The present study aims to assess the association of total thyroxine (TT4) levels in newborns with weekly prenatal exposure to PM2.5 and NO2 and to identify sensitivity windows to exposure to air pollution in different developmental stages. METHODS: This prospective cohort study included mother-child pairs from the INMA-Gipuzkoa project. Specifically, 463 mother-child pairs with data on PM2.5 and NO2 exposure during pregnancy and TT4 levels at birth were included. PM2.5 and NO2 levels were measured by high-volume aerosol samplers and passive samplers respectively during the women's pregnancies. TT4 levels were measured in heel-prick blood samples from infants. Data on maternal and infant covariates were gathered through questionnaires administered in the first and third trimesters of pregnancy and review of clinical records. Potential associations of PM2.5 and NO2 with TT4 levels over the entire pregnancy was assessed by linear regression models and DLMs were used to identify susceptibility windows. RESULTS: The exposure of pregnant women to PM2.5 during pregnancy was positively associated with infant TT4 level at birth (ß [95% CI] = 0.198 [0.091, 0.305]. DLMs identified three different sensitivity windows, one in the periconceptional period with a negative association between PM2.5 exposure and TT4 levels at birth, and a second (weeks 12-17) and a third one (weeks 31-37) with a positive association. In addition, the later the exposure, the stronger the association. In contrast, no association was observed between NO2 exposure and TT4 levels. CONCLUSIONS: The results indicate that prenatal exposure to PM2.5 could lead to a thyroid function impairment in newborns.

Rationalisation of the caesarean section rate in a tertiary referral hospital using the Robson classification.

The aim of this study was to implement the Robson Ten Groups Classification System (RTGCS) to identify the main contributors to the caesarean section (CS) rate and to evaluate whether the introduction of a plan of obstetrical interventions reduced this rate. An observational retrospective cross-sectional study was conducted during two time periods at Alicante University General Hospital. In the pre-implementation period (2009-2012), RTGCS was applied to identify the main groups contributing to the overall CS rate. In the post-implementation period (2013-2017), RTGCS was applied again to identify changing trends in CS rates. In all, 11,034 deliveries during the pre-intervention period and 11,453 during the post-intervention period were analysed. The overall CS rate was 23.9% and 20.9%, respectively. There were no changes in perinatal outcomes. In the post-intervention period, there was a significant decrease of the CS rate in the groups of targeted interventions 1, 2, 3, 4, 5, and 8B.Impact statementWhat is already known on this subject? High CS rates are becoming a public health problem because of risks, costs, excessive medicalisation, and abuse of resources. RTGCS provides a framework for auditing and analysing CS rates.What do the results of this study add? RTGCS can identify the groups that have the greatest impact on the CS rate and monitor changes in it consequent to policy changes.What are the implications of these findings for clinical practice? The introduction of a strategic plan with evidence-based clinical interventions may have a greater effect on the CS rate than other features justifying the increase in the incidence of CS.

Evolving options for the treatment of cluster headache.

PURPOSE OF REVIEW: Cluster headache is a neurological disorder that patients consider the most severe pain they experience. Recognizing new treatments provides opportunities to advance current management. RECENT FINDINGS: In contrast to the classic treatments, new options narrow in on the therapeutic target and are better tolerated. Calcitonin gene-related peptide (CGRP) pathway blockade with monoclonal antibodies (MABs), specifically the CGRP MAB galcanezumab, represents an important advance for episodic cluster headache, reducing the number of attacks during a bout. Neuromodulation strategies aimed at anatomical structures involved in the pathophysiology of cluster headache, such as the sphenopalatine ganglion and the vagus nerve, have proved effective in reducing the pain intensity and the number of attacks, and also to be safe and well tolerated. SUMMARY: Our understanding of the pathophysiology of cluster headache and its management continues to grow. Novel treatments have appeared from research, such as neuromodulation and CGRP monoclonal antibodies. Nonetheless, chronic cluster headache and designing trials that select the correct sham in evaluating devices remain challenging.

Targeting CGRP and 5-HT1F Receptors for the Acute Therapy of Migraine: A Literature Review.

OBJECTIVE: To review and highlight current literature on emerging acute migraine treatments, focusing on CGRP receptor antagonists, gepants, and 5-HT1F receptor agonists (ditans). BACKGROUND: Current acute migraine therapy consists of nonspecific analgesia and triptans. Limitations to these medicines, including lack of efficacy in many patients, side effects and the contraindication of triptans in patients with cardiovascular disease, suggest that there is an unmet need for new treatments. Studies of serotonin pharmacology led to the development of triptans, 5-HT1B/1D receptor agonists, some of which have actions at the 5-HT1F receptor. Exploration of the role of calcitonin gene-related peptide (CGRP) has resulted in the development of CGRP receptor antagonists. METHOD: The authors performed a literature search of Pubmed and Cochrane databases as well as reviewed abstracts presented at meetings: American Headache Society, American Academy of Neurology, European Headache Federation and the Migraine Trust International Symposium, as well as on-line sources. The authors briefly detail the relevant migraine pathophysiology pertaining to 5-HT1F receptor and the CGRP pathway relevant to acute therapies. Recent clinical trials of acute therapies in which 5-HT1F receptor agonists or CGRP receptor antagonists were studied are summarized. RESULTS: Two 5-HT1F receptor agonists have reached phase II clinical trials. One, lasmiditan, has completed 2 phase III clinical trials, demonstrating a significant effect for pain freedom and most bothersome symptom at 2 hours. Among the 6 gepants tested for the acute treatment of migraine to date, after issues for some of hepatic safety or efficacy, 2 CGRP receptor antagonists, rimegepant and ubrogepant, have completed phase III trials showing efficacy and safety. CONCLUSION: Current available therapies have either been nonspecific or had important limitations, including in patients with cardiovascular risk factors. Phase III clinical trials of lasmiditan, rimegepant and ubrogepant all met their primary endpoints, so the options for migraine-targeted acute therapy will likely soon increase.

Prenatal exposure to PM2.5 and NO2 and sex-dependent infant cognitive and motor development.

BACKGROUND: Prenatal exposure to air pollutants including particulate matter (<2.5 µm of diameter,PM2.5)and nitrogen dioxide (NO2) has been identified as a potential risk factor for neuropsychological developmental and mental health disorders. OBJECTIVE: This study aimed to analyze the associations between prenatal PM2.5 and NO2 exposure and cognitive functions in children at 4-6 years of age, including sex differences, and the modification effect of the duration predominant breastfeeding these associations. DESIGN: This study was conducted as part of the INMA project, a population-based birth cohort study in Spain (n = 1119). Each of the pregnant mothers was assigned a prenatal exposure to PM2.5 and NO2 for their whole pregnancy based on their place of residence. At the 4-6 year-old follow-up, infants' neuropsychological development was assessed using McCarthy scales: Verbal, Perceptive-Manipulative, Numeric, General Cognitive, Memory and Motor (gross and fine). Between 6 and 14 months of age, information concerning breastfeeding was gathered with a questionnaire. Regression analyses were performed to estimate the associations between exposure and outcomes, accounting for potential confounders. The analyses were stratified by child sex and breastfeeding duration. RESULTS: The majority of coefficients for the different cognitive domains were negative either for PM2.5 and NO2, though none was statistically significant. After stratifying by sex, the associations become even more negative for boys, with some of the associations becoming statistically significant (memory both for PM2.5 and NO2), and global cognition and verbal for NO2. Duration of predominant breastfeeding was not found to have a modifying effect. CONCLUSIONS: These findings suggest a sex-dependent effects on neuropsychological development at 4-6 years of age, with a greater vulnerability in boys, specifically in domains related to memory, verbal and general cognition. No modifying effect was observed for duration of predominant breastfeeding.

The COPD Comorbidome in the Light of the Degree of Dyspnea and Risk of Exacerbation.

The BODE group designed a bubble chart, analogous to the solar system, which depicts the prevalence of each disease and its association with mortality and called it a "comorbidome". Although this graph was used to represent mortality and, later, the risk of needing hospital admission, it was not applied to visualize the association between a set of comorbidities and the categories of the GOLD 2017 guidelines, neither according to the degree of dyspnea nor to the risk of exacerbation. For the purpose of knowing to which extent each comorbidity associates with each of the two conditions-most symptomatic group (groups B and D) and highest risk of exacerbation (groups C and D)-we performed a analysis based on the comorbidome. 439 patients were included. Cardiovascular comorbidity (especially cardiac and renal disease) is predominantly observed in patients with a higher degree of dyspnea, whereas bronchial asthma and stroke occur more frequently in subjects at higher risk of exacerbation. This is the first time that the comorbidome is presented based on the categories of the GOLD 2017 document, which we hope will serve as a stimulus for scientific debate.

Effect of the Use of Purified Grape Pomace as a Fining Agent on the Volatile Composition of Monastrell Wines.

(1) Background: The lack of viable alternatives for the industrial exploitation of grape pomace is one of the reasons why it is considered a serious environmental pollutant. However, as a byproduct, it could be used as a fining agent, since previous studies have shown that it is able to eliminate undesirable substances in wine. However, the little information available does not describe its effect on wine aroma. (2) Methods: Purified grape pomace extracts were used for fining a red wine and their effect on the volatile compounds of the wine was assessed, comparing the results with those obtained with different commercial fining agents. (3) Results: The results showed how purified grape pomace decreased the total volatile content of a wine to a similar extent as other fining products, such as yeast extracts or gelatin. Among the different families of volatile compounds analyzed, only total esters and terpenes differed from the levels recorded for a control wine, being slightly lower. No statistical differences were found for the rest of the volatile compounds (alcohols, carbonyl, lactones, and acids) compared with the levels measured in control wine. (4) Conclusions: The results suggest that purified grape pomace could be used as a non-allergenic wine fining agent.

Health Status in Patients with COPD According to GOLD 2017 Classification: Use of the COMCOLD Score in Routine Clinical Practice.

The COMCOLD score was developed to quantify the impact of comorbidities on health status in patients with chronic obstructive pulmonary disease (COPD). The objective of this study is to evaluate the association between health status in outpatients with COPD according to COMCOLD score and the GOLD 2017 groups according to symptoms (B and D vs. A and C) and exacerbations (C and D vs. A and B). 439 patients were included. The average score was 2.4 ± 3. 48% of cases had a COMCOLD score >0. The most symptomatic patients (B and D vs. A and C) had a higher score: 3 ± 3.3 vs. 1.3 ± 2.1 (p < 0.001), in contrast with the groups with a higher risk of exacerbation (C and D vs. A and B) in which there was no significant difference: 3 ± 3.5 vs. 2.2 ± 3.0 (p = 0.055). The most symptomatic patients (B and D) showed a greater prevalence of depression, peripheral artery disease and heart disease with an adjusted OR of 3.04 [CI95%: 1.36; 6.86], 2.49 [CI95%: 1.17; 5.29], and 4.41 [CI95%: 2.50; 7.75], respectively. Moreover, no relationship was found between the comorbidities defined by the COMCOLD score and the GOLD 2017 groups with the greatest risk of exacerbation (C and D). The greatest effect on health status was found in those patients with COPD belonging to the most symptomatic groups (B and D), with depression, peripheral artery disease, and heart disease being the main comorbidities involved.

Technological Implications of Modifying the Extent of Cell Wall-Proanthocyanidin Interactions Using Enzymes.

The transference and reactivity of proanthocyanidins is an important issue that affects the technological processing of some fruits, such as grapes and apples. These processes are affected by proanthocyanidins bound to cell wall polysaccharides, which are present in high concentrations during the processing of the fruits. Therefore, the effective extraction of proanthocyanidins from fruits to their juices or derived products will depend on the ability to manage these associations, and, in this respect, enzymes that degrade these polysaccharides could play an important role. The main objective of this work was to test the role of pure hydrolytic enzymes (polygalacturonase and cellulose) and a commercial enzyme containing these two activities on the extent of proanthocyanidin-cell wall interactions. The results showed that the modification promoted by enzymes reduced the amount of proanthocyanidins adsorbed to cell walls since they contributed to the degradation and release of the cell wall polysaccharides, which diffused into the model solution. Some of these released polysaccharides also presented some reactivity towards the proanthocyanidins present in a model solution.

A Randomized Control Trial of Dexketoprofen/Vitamin B (Thiamine, Pyridoxine and Cyanocobalamin) Fixed-Dose Combination in Post-Traumatic Grade I-II Cervical Sprains.

BACKGROUND: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders. OBJECTIVE: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains. METHODS: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0. RESULTS: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC. CONCLUSIONS: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains. CLINICAL TRIALS REGISTRATION: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).

Normal pressure hydrocephalus mimicking Alzheimer's disease: such an infrequent case?

Normal pressure hydrocephalus (NPH) is an age-related condition frequently associated with degenerative and vascular brain pathologies. However, cases of NPH with no concomitant brain pathology have been described with important implications in terms of early detection and treatment. We present a case of NPH that commenced with cognitive deterioration similar to Alzheimer's disease (AD). Motor manifestations (i.e., falls and gait dysfunction) appeared 2.5 years after the initiation of memory problems. Apart from ventricular enlarging, no prominent pathologies were found at brain examination. The prevalence of cases of NPH presenting with memory problems may be underestimated given the traditional view of NPH displaying a clinical triad of gait dysfunction, mental decline of "subcortical" appearance, and incontinence. Careful examination of the structural neuroimaging study in the initial assessment and during follow-up could help in diagnosis. Further research on prevalence and detection of "pure" NPH initially resembling AD is warranted.

Risk of episiotomy and perineal lacerations recurring after first delivery.

BACKGROUND: To assess whether the presence of an episiotomy or spontaneous perineal trauma at the first delivery increases the risk of perineal trauma at the following one. METHODS: We studied 2,695 women who gave birth twice at Virgen de las Nieves University Hospital of Granada, Spain. All second deliveries were from 2004 to 2011 and prenatal database records were used to obtain information about the first deliveries. All births, first and second, were single, vaginal, unassisted, and in a cephalic presentation. Two groups were made as follows: Intact perineum (no perineal trauma or first-degree spontaneous tear at the first delivery) and perineal trauma (episiotomy or second-degree or higher spontaneous tear at the first delivery). Both groups were compared according to the degree of perineal trauma at the second delivery. RESULTS: Women included in the perineal trauma group were significantly older and a higher proportion was attended by a midwife with an obstetrician present in the delivery room. No differences were observed according to gestational age, epidural analgesia or fetal birth weight. Adjusting for these possible compounding factors and the year of birth, the risk of undergoing a second-degree or higher spontaneous tear at their next delivery was fivefold (adjusted OR 5.15, 95% CI 3.11-8.54), and the risk of undergoing an episiotomy in the second delivery was threefold (adjusted OR 3.20, 95% CI 2.19-4.69) for the perineal trauma group. CONCLUSION: The risk of undergoing a spontaneous perineal tear or an episiotomy in the second delivery is increased by the practice of episiotomy in the first one.