Transcranial direct current stimulation over the left posterior temporal lobe modulates semantic control: Evidence from episodic memory distortions.

Evidence accumulates to show that semantic cognition requires, in addition to semantic representations, control processes that regulate the accessibility and use of semantic knowledge in a task- and time-appropriate fashion. Semantic control has been recently proposed to rely on a distributed network that includes the posterior temporal cortex. Along these lines, recent meta-analyses of neuroimaging data and studies with patients suffering from semantic aphasia have suggested that the left posterior middle temporal gyrus (pMTG) is critically involved whenever situational context must constrain semantic retrieval. In the present experiment, we used transcranial direct current stimulation over the left posterior temporal lobe in an attempt to interfere with semantic control while participants performed a DRM task, a procedure for inducing conceptually-based false recognition that is contingent on both activation and control processes. Paralleling findings with patients suffering from brain damage restricted to the temporoparietal cortex, anodal stimulation (relative to sham stimulation) resulted in increased false recognition but intact true recognition. These findings fit well with the idea that the left pMTG is a key component of a semantic control network, the alteration of which results in memory performance that is affected by the intrusion of contextually-inappropriate semantic information.

Analysis of the determinants of sleep quality in a Spanish population: a study protocol for a cross-sectional study.

INTRODUCTION: Sleep problems are a growing public health concern being related, among others, to an increased risk of cardiovascular diseases or worse cognitive functioning. In addition, they can affect aspects related to personal motivation and quality of life. However, very few studies have analysed the possible determinants of sleep quality in the adult population as a whole, establishing patterns based on these determinants.The objectives are to evaluate the determinants of sleep quality in a representative sample of the general adult population between 25 and 65 years old, and to establish patterns of sleep quality based on lifestyles, psychological factors, morbidities, sociodemographic variables, biological markers and other possible determinants. METHODS AND ANALYSIS: Descriptive observational cross-sectional study. The study population will include a representative sample of 500 people between 25 and 65 years old from the cities of Salamanca and Ávila (Spain) selected by random sampling stratified by age groups and sex. A 90-minute visit will be performed, during which sleep quality will be assessed. The variables collected will be: morbidity, lifestyles (physical activity, diet, toxic habits), psychological factors (depression, stress, occupational stress and anxiety), socioeconomic and work-related variables, habitability conditions of the habitual residence and rest area, screen time, relaxation techniques and melatonin as a biological marker related to sleep quality. DISCUSSION: With the results of this work, improved interventions for behaviour modification could be designed, as well as intervention and education programmes or other research aimed at improving sleep quality. ETHICS AND DISSEMINATION: This study has a favourable opinion from the Ethics Committee for Drug Research of the Health Areas of Salamanca and Ávila (CEim Code: PI 2021 07 815). The results of this study will be published in international impact journals of different specialties. TRIAL REGISTRATION NUMBER: NCT05324267.

First Confirmed Diagnosis of Nocardioform Placentitis (Amycolatopsis lexingtonensis) in South America.

Nocardioform placentitis is a pathologically unique form of placental disease first diagnosed in central Kentucky in the mid-80s. Since then, the occurrence of nocardioform placentitis in the region has varied over the years, from sporadic cases to outbreaks. The disease has been sporadically detected in other countries and has not been confirmed in South America. A 13-year-old multiparous Mangalarga delivered a healthy filly at 340d gestation. The mare passed the fetal membranes 33 minute after foaling. Gross examination of the fetal membranes identified two focal lesions on the chorionic surface consistent with focal mucoid placentitis. Histopathologic evaluation revealed hyperplasia and degeneration of the allantoic mesoderm, intense mononuclear inflammatory infiltrates with marked lymphocytes and plasma, and occasional macrophages and neutrophils in the microvilli. Necrotic debris and exudate were identified in the chorionic epithelium, with macrophages, plasma cells, and neutrophils confirming the diagnosis of focal mucoid placentitis. The exudate culture revealed white, firm, punctiform colonies of ∼1 mm diameter. Gram staining revealed bacilli with rounded ends and branching aspect typical of actinomycetes. PCR using primers for the 16S rRNA identified the genera of bacteria as Amycolatopsis. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis identified the isolate as Amycolatopsis lexingtonensis. In conclusion, we described the first confirmed case of nocardioform placentitis in South America. The present case was associated with the birth of a full-term healthy live foal; this result is consistent with Amycolatopsis spp and, in this case, was caused by A. lexingtonensis.

Oxidative state in equine neonates: Anti- and pro-oxidants.

BACKGROUND: In newborns, exposure to the extrauterine environment with high oxygen tension and sudden pulmonary adaptation leads to an increase in reactive oxygen species (ROS). ROS have several physiological roles, which are essential for neonatal development, however, when unbalanced, these highly unstable molecules can cause cellular destabilisation, compromising vital processes. OBJECTIVES: To characterise the oxidative status in healthy equine neonates, evaluating an indicator of lipid peroxidation and both enzymatic and nonenzymatic antioxidant systems, during the first week of life. STUDY DESIGN: Experimental cohort. METHODS: Twenty-four foals were evaluated, with blood collections performed at 5 minutes, 12, 72 and 168 hours after birth. The degree of lipid peroxidation was quantified using Thiobarbituric Acid Reactive Substances (TBARS). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic activities, and total, conjugated and unconjugated serum bilirubin levels were also analysed. Comparisons were performed using ANOVA followed by a Tukey's test. Additionally, dependent variables were also evaluated with Pearson's correlation tests. RESULTS: Higher GPx activity was observed at 12 and 72 hours when compared to 5 minutes. An increase in TBARS levels was found at 5 minutes after birth, followed by a decrease at 72 hours and stabilisation through subsequent moments until 168 hours after birth. No differences were observed in SOD activity when comparing the four time points. Bilirubin concentrations were lower at 5 minutes after birth and total and unconjugated bilirubin increased at 12 hours and decreased between 72 and 168 hours after birth. CONCLUSIONS: Lipid peroxidation at birth was high, suggesting an increase in ROS levels relating to physiological events in neonatal adaptation. Antioxidant systems, involving unconjugated bilirubin and GPx, were activated and these biomolecules act concomitantly to reduce ROS levels, thus maintaining oxidative homeostasis. Overall, our results suggest a pro-oxidant balance during the first 168 hours after birth in equine neonates.

A set of 750 words in Spanish characterized in two survival-related dimensions: avoiding death and locating nourishment.

With the aim of finding quantitative indicators of the survival relevance for a set of concrete concepts, a subjective rating task was administered to a large sample of college students (N = 300). In the rating task, participants used a five-point scale to rate 750 concepts in one of two survival-relevant dimensions, providing their own judgment about the relevance of each concept in a situation in which either avoiding death (AD) or obtaining food (OF) was of importance. The subjective ratings showed high stability and reliability and showed varied patterns of association to potentially relevant concept-defining variables, with correlational analyses showing both commonalities and differences between the two rated dimensions. Regression analyses indicated that, while not likely to modulate word accessibility, survival ratings were related to certain conceptual properties that could be especially sensitive for threat detection. The collected data set provides normative information that can be of use in manipulating and controlling verbal stimuli in future research focusing on adaptive properties of episodic memory and other aspects of the human cognitive system. The complete norms are available for downloading at Open Science Framework ( https://osf.io/sf9mb/ ).

Absence of posture-dependent and posture-congruent memory effects on the recall of action sentences.

In two experiments with large samples of participants, we explored contextual memory effects associated with body posture, which was considered a physical and proprioceptive context and, therefore, potentially relevant to the encoding and retrieval of information. In Experiment 1 (N = 128), we studied the effect of context dependence on memory by manipulating the body posture adopted by the participants during the incidental encoding and subsequent recall of a series of action sentences not intrinsically associated with particular body postures (e.g., "to put on a pair of glasses", "to look at a postcard"). Memory performance was not affected by context manipulation, as reflected by the absence of significant differences between remembering while in the posture adopted at study or in a different posture. Experiment 2 (N = 85) was designed to analyze context congruency memory effects, and for that purpose we manipulated the participants' body posture during the recall of sentences that described actions usually performed in body postures that were congruent or incongruent with the posture of the participants (e.g., recalling the sentence "to travel by taxi" while sitting or while standing). A content-neutral posture (lying) was used for the incidental encoding phase. Memory performance was not affected by contextual congruency at the time of recall, as evidenced by the lack of significant differences between recalling in a posture congruent with the content to be recalled and recalling in an alternative posture. Bayesian analyses supported the strength of null findings in the two experiments, adding to the evidence that, when taken together, the results in this study clearly failed to show contextual memory effects of body posture on the recall of action-related verbal statements.

Non-synonymous WNT16 polymorphisms alleles are associated with different osteoarthritis phenotypes.

Hereditary factors have a strong influence on osteoarthritis (OA). The Wnt pathway is involved in bone and cartilage homeostasis. Hence, we hypothesized that allelic variations of WNT16 could influence the OA phenotype. We studied 509 Caucasian patients undergoing joint replacement due to severe primary OA. Radiographs were used to classify the OA as atrophic or hypertrophic. Two nonsynonymous polymorphisms of WNT16 (rs2707466 and rs2908004) were analyzed. The association between the genotypes and the OA phenotype was analyzed by logistic regression and adjusted for age and body mass index. A genotype-phenotype association was found in the sex-stratified analysis. Thus, there was a significant difference in the genotypic frequencies of rs2707466 between hypertrophic and atrophic hip OA in males (p = 0.003), with overrepresentation of G alleles in the hypertrophic phenotype (OR 2.08; CI 1.28-3.38). An association in the same direction was observed between these alleles and the type of knee OA, with G alleles being more common in the hypertrophic than in atrophic knee phenotypes (p = 0.008; OR 1.956, CI 1.19-3.19). Similar associations were found for the rs2908004 SNP, but it only reached statistical significance for knee OA (p = 0.017; OR 0.92, CI 0.86-0.989). This is the first study attempting to explore the association of genetic variants with the OA phenotype. These data suggest the need to consider the OA phenotype in future genetic association studies of OA.

The processing of semantic relatedness in the brain: Evidence from associative and categorical false recognition effects following transcranial direct current stimulation of the left anterior temporal lobe.

A dominant view of the role of the anterior temporal lobe (ATL) in semantic memory is that it serves as an integration hub, specialized in the processing of semantic relatedness by way of mechanisms that bind together information from different brain areas to form coherent amodal representations of concepts. Two recent experiments, using brain stimulation techniques along with the Deese-Roediger-McDermott (DRM) paradigm, have found a consistent false memory reduction effect following stimulation of the ATL, pointing to the importance of the ATL in semantic/conceptual processing. To more precisely identify the specific process being involved, we conducted a DRM experiment in which transcranial direct current stimulation (anode/cathode/sham) was applied over the participants' left ATL during the study of lists of words that were associatively related to their non-presented critical words (e.g., rotten, worm, red, tree, liqueur, unripe, cake, food, eden, peel, for the critical item apple) or categorically related (e.g., pear, banana, peach, orange, cantaloupe, watermelon, strawberry, cherry, kiwi, plum, for the same critical item apple). The results showed that correct recognition was not affected by stimulation. However, an interaction between stimulation condition and type of relation for false memories was found, explained by a significant false recognition reduction effect in the anodal condition for associative lists that was not observed for categorical lists. Results are congruent with previous findings and, more importantly, they help to clarify the nature and locus of false memory reduction effects, suggesting a differential role of the left ATL, and providing critical evidence for understanding the creation of semantic relatedness-based memory illusions.

Differential analysis of genome-wide methylation and gene expression in mesenchymal stem cells of patients with fractures and osteoarthritis.

Insufficient activity of the bone-forming osteoblasts leads to low bone mass and predisposes to fragility fractures. The functional capacity of human mesenchymal stem cells (hMSCs), the precursors of osteoblasts, may be compromised in elderly individuals, in relation with the epigenetic changes associated with aging. However, the role of hMSCs in the pathogenesis of osteoporosis is still unclear. Therefore, we aimed to characterize the genome-wide methylation and gene expression signatures and the differentiation capacity of hMSCs from patients with hip fractures. We obtained hMSCs from the femoral heads of women undergoing hip replacement due to hip fractures and controls with hip osteoarthritis. DNA methylation was explored with the Infinium 450K bead array. Transcriptome analysis was done by RNA sequencing. The genomic analyses revealed that most differentially methylated loci were situated in genomic regions with enhancer activity, distant from gene bodies and promoters. These regions were associated with differentially expressed genes enriched in pathways related to hMSC growth and osteoblast differentiation. hMSCs from patients with fractures showed enhanced proliferation and upregulation of the osteogenic drivers RUNX2/OSX. Also, they showed some signs of accelerated methylation aging. When cultured in osteogenic medium, hMSCs from patients with fractures showed an impaired differentiation capacity, with reduced alkaline phosphatase activity and poor accumulation of a mineralized matrix. Our results point to 2 areas of potential interest for discovering new therapeutic targets for low bone mass disorders and bone regeneration: the mechanisms stimulating MSCs proliferation after fracture and those impairing their terminal differentiation.

Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in prevalent skeletal disorders.

We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in osteoarthritis. We aimed to confirm those results by analyzing ß-catenin levels and explored potential genetic and epigenetic mechanisms involved. ß-Catenin gene expression and nuclear levels were analyzed by real time PCR and confocal immunofluorescence. Increased nuclear ß-catenin was found in osteoblasts isolated from patients with osteoarthritis (99 ± 4 units vs. 76 ± 12, p=0.01, n=10), without differences in gene transcription, which is consistent with a post-translational down-regulation of ß-catenin and decreased Wnt pathway activity. Twenty four single nucleotide polymorphisms (SNPs) of genes showing differential expression between fractures and osteoarthritis (WNT4, WNT10A, WNT16 and SFRP1) were analyzed in DNA isolated from blood of 853 patients. The genotypic frequencies were similar in both groups of patients, with no significant differences. Methylation of Wnt pathway genes was analyzed in bone tissue samples (15 with fractures and 15 with osteoarthritis) by interrogating a CpG-based methylation array. Six genes showed significant methylation differences between both groups of patients: FZD10, TBL1X, CSNK1E, WNT8A, CSNK1A1L and SFRP4. The DNA demethylating agent 5-deoxycytidine up-regulated 8 genes, including FZD10, in an osteoblast-like cell line, whereas it down-regulated other 16 genes. In conclusion, Wnt activity is reduced in patients with hip fractures, in comparison with those with osteoarthritis. It does not appear to be related to differences in the allele frequencies of the Wnt genes studied. On the other hand, methylation differences between both groups could contribute to explain the differences in Wnt activity.

Role of BMPs in the regulation of sclerostin as revealed by an epigenetic modifier of human bone cells.

Sclerostin, encoded by the SOST gene, is specifically expressed by osteocytes. However osteoblasts bear a heavily methylated SOST promoter and therefore do not express SOST. Thus, studying the regulation of human SOST is challenged by the absence of human osteocytic cell lines. Herein, we explore the feasibility of using the induction of SOST expression in osteoblasts by a demethylating agent to study the mechanisms underlying SOST transcription, and specifically, the influence of bone morphogenetic proteins (BMPs). Microarray analysis and quantitative PCR showed that AzadC up-regulated the expression of several BMPs, including BMP-2, BMP-4 and BMP-6, as well as several BMP downstream targets. Recombinant BMP-2 increased the transcriptional activity of the SOST promoter cloned into a reporter vector. Likewise, exposing cells transfected with the vector to AzadC also resulted in increased transcription. On the other hand, inhibition of the canonical BMP signaling blunted the effect of AzadC on SOST. These results show that the AzadC-induced demethylation of the SOST promoter in human osteoblastic cells may be a valuable tool to study the regulation of SOST expression. As a proof of concept, it allowed us to demonstrate that BMPs stimulate SOST expression by a mechanism involving BMPR1A receptors and downstream Smad-dependent pathways.

Genetic polymorphisms of the Wnt receptor LRP5 are differentially associated with trochanteric and cervical hip fractures.

Epidemiological studies suggest that cervical and trochanteric hip fractures have different pathogenesis. We tested the hypothesis that genetic factors have different influences on both types of fractures. Ten polymorphisms of genes known to play an important role in skeletal homeostasis [estrogen receptor alpha (ESR1), aromatase (CYP19A1), type I collagen (COL1A1), and lipoprotein receptor-related protein 5 (LRP5)] were analyzed in 471 Spanish patients with fragility hip fractures. Two polymorphisms of the LRP5 gene (rs7116604 and rs3781600) were associated with the type of fracture (P = 0.0085 and 0.0047, respectively). The presence of rare alleles at each locus was associated with trochanteric fractures over cervical fractures (OR = 1.7 in individuals with at least one rare allele at rs7116604 or rs3781600 loci in comparison with the common homozygotes). Considering individuals bearing the four common alleles as reference, the OR for trochanteric fractures was 1.6 in those with one or two rare alleles and 7.5 in those with three or four rare alleles (P for trend = 0.0074), which is consistent with an allele-dosage effect. There were no significant differences in the frequency distributions of the ESR1, CYP19A1, and COL1A1 genotypes between trochanteric and cervical fractures in either the original group or an extended group of 818 patients. These results suggest that LRP5 alleles influence the type of hip fractures. They support the view that different genetic factors are involved in cervical and trochanteric fractures, which should be taken into consideration in future genetic association studies.

Biodiversity of Archaea and floral of two inland saltern ecosystems in the Alto Vinalopó Valley, Spain.

BACKGROUND: The extraction of salt from seawater by means of coastal solar salterns is a very well-described process. Moreover, the characterization of these environments from ecological, biochemical and microbiological perspectives has become a key focus for many research groups all over the world over the last 20 years. In countries such as Spain, there are several examples of coastal solar salterns (mainly on the Mediterranean coast) and inland solar salterns, from which sodium chloride is obtained for human consumption. However, studies focused on the characterization of inland solar salterns are scarce and both the archaeal diversity and the plant communities inhabiting these environments remain poorly described. RESULTS: Two of the inland solar salterns (termed Redonda and Penalva), located in the Alto Vinalopó Valley (Alicante, Spain), were characterized regarding their geological and physico-chemical characteristics and their archaeal and botanical biodiversity. A preliminary eukaryotic diversity survey was also performed using saline water. The chemical characterization of the brine has revealed that the salted groundwater extracted to fill these inland solar salterns is thalassohaline. The plant communities living in this environment are dominated by Sarcocornia fruticosa (L.) A.J. Scott, Arthrocnemum macrostachyum (Moris) K. Koch, Suaeda vera Forsk. ex Gmelin (Amaranthaceae) and several species of Limonium (Mill) and Tamarix (L). Archaeal diversity was analyzed and compared by polymerase chain reaction (PCR)-based molecular phylogenetic techniques. Most of the sequences recovered from environmental DNA samples are affiliated with haloarchaeal genera such as Haloarcula, Halorubrum, Haloquadratum and Halobacterium, and with an unclassified member of the Halobacteriaceae. The eukaryote Dunaliella was also present in the samples. CONCLUSIONS: To our knowledge, this study constitutes the first analysis centered on inland solar salterns located in the southeastern region of Spain. The results obtained revealed that the salt deposits of this region have marine origins. Plant communities typical of salt marshes are present in this ecosystem and members of the Halobacteriaceae family can be easily detected in the microbial populations of these habitats. Possible origins of the haloarchaea detected in this study are discussed.

Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians.

BACKGROUND: Despite their great impact, few genetic association studies have used hip fractures as an endpoint. However, the association of two polymorphisms on intron 4 of estrogen receptor alpha (ESR1) with hip fractures was recently reported in a Chinese population. The aim of this study was to investigate whether such association is also present in Caucasians. METHODS: We analyzed those two SNPs and another neighbour SNP located on the exon 4 of ESR1 in 787 patients with hip fractures and 953 controls from Spain. RESULTS: The allelic frequencies differed markedly from those reported in Asian populations. Nevertheless, haplotypes including the rs3020314 and rs1884051 loci in intron 4 showed a significant association with hip fractures (omnibus test p = 0.006 in the whole group and 0.00005 in women). In the sex-stratified analysis, the association was significant in females, but not in males. In women, the CA haplotype appeared to have a protective influence, being present in 6.5% of the controls, but only in 3% of patients with fractures (odds ratio 0.39; 95% confidence interval 0.26-0.59; estimated population preventive fraction 3.5%). The inclusion of the rs1801132 SNP of exon 4 further increased the statistical significance of the association (odds ratio 0.17; 95% CI 0.08-0.37; p = 0.00001). Each SNP appeared to contribute independently to the association. No genotype-related differences in gene expression were found in 42 femoral bone samples. CONCLUSIONS: This study confirms the association of some polymorphisms in the region of exon 4/intron 4 of ESR1 and hip fractures in women. However, there are marked differences in allele frequencies between Asian and Caucasian populations.

Aromatase expression in osteoarthritic and osteoporotic bone.

OBJECTIVE: Estrogen deprivation is a central mechanism in the development of osteoporosis with aging. Results from recent studies also suggest the involvement of estrogens in the pathophysiology of osteoarthritis (OA). Aromatization of androgenic precursors in peripheral tissue is the main source of estrogens in postmenopausal women and in men. However, the importance of aromatase expression in bone is a subject of controversy. This study was undertaken to determine aromatase expression in bone samples from patients with hip fracture and patients with OA. METHODS: We studied 104 patients with hip fracture (n = 60) or primary hip OA (n = 44). Aromatase expression was determined in trabecular bone samples from the femoral neck and in osteoblast cultures grown by the primary explant technique (n = 62), using real-time reverse transcriptase-polymerase chain reaction. RESULTS: Aromatase RNA was detected in bone samples at levels similar to those found in adipose tissue. Transcript levels were significantly lower in bone tissue samples obtained from patients with OA than in those obtained from patients with fracture (P = 0.00001). Likewise, primary cultures of osteoblast cells from OA patients revealed lower aromatase expression than those of cells from fracture patients (P = 0.012). Results were independent of age or sex differences. CONCLUSION: Our findings indicate that the aromatase gene is expressed in bone tissue in high amounts, similar to those found in adipose tissue, but transcript levels are lower in tissue samples and osteoblast cultures from patients with OA than in those from patients with hip fracture. Since estrogens may help to prevent local cartilage degradation, it can be speculated that such a reduced expression of aromatase could facilitate the development of OA.

Acute pancreatitis mimicking acute inferior myocardial infarction.

A 56-year-old man presented with acute pancreatitis and electrocardiographic abnormalities, suggesting acute inferior myocardial infarction. An emergent coronary angiogram showed normal coronary arteries. The clinical significance and therapeutic implications of this rare finding are discussed.

Association of the F352V variant of the Klotho gene with bone mineral density.

Klotho gene codes for a protein with glucuronidase activity and is thought to influence bone and vascular homeostasis. We studied the relationship of a common T/G polymorphism, resulting in a phenylalanine (F) to valine (V) substitution at aminoacid position 352, with bone mineral density (BMD) and osteoporotic fractures. The study group comprised 914 Spanish women, including 438 control subjects, 190 patients with osteoporosis, 198 with hip fractures, and 88 patients with severe osteoarthritis. BMD was measured by DEXA in 540 women from the control and osteoporosis groups. Allele frequencies were 86% and 14%, for the F and V alleles, respectively. In comparison with the most common FF genotype, postmenopausal women with FV/VV genotypes had higher hip BMD (femoral neck: 0.673 +/- 0.011 vs. 0.644 +/- 0.006 g/cm(2); P = 0.02; total hip: 0.807 +/- 0.014 vs. 0.774 +/- 0.008 g/cm(2); P = 0.03). Klotho alleles explained about 1.5% of BMD variance, but were not associated to the risk of osteoporotic spine or hip fractures. The Klotho genotype was not associated to BMD in premenopausal women. In conclusion, the F352V Klotho polymorphism is associated with BMD in postmenopausal women, suggesting that Klotho gene variants influence skeletal aging.

Trend in hip fracture epidemiology over a 14-year period in a Spanish population.

Spain lacks detailed data on hip fracture trends despite being the country with the greatest increase in the pensioner-to-provider ratio in Europe. We reproduced a study on hip fracture incidence in a region of northern Spain (Cantabria) carried out 14 years ago to determine whether a secular trend to change is taking place. If such a trend could be found, our objective was to determine whether the effect is solely due to ageing or whether additional variables are involved. We assessed the incidence of hip fracture in patients aged > or =50 years through clinical records from Emergency Units and Orthopedic Surgical Units of all hospitals in the region of Cantabria in 1988 and 2002. A total of 318 new cases of hip fracture were recorded in 1988 and 490 in 2002 (54% increase; p<0.001). No significant changes were noticed following an adjustment for age. Women accounted for the increase in crude hip fracture incidence [246 women and 72 men suffered a hip fracture in 1988 compared to 404 women and 86 men in 2002 (64% increase in women and 19% increase in men; p<0.005 and not significant, respectively)]. The female:male ratio was 3.4 in 1988 versus 4.7 in 2002; following age-adjustment, no significant changes were found (1.8 in 1988 and 1.9 in 2002). The increase in crude hip fracture incidence was greater at cervical (versus trochanteric) sites. Patient residence, time of the year, site of fracture, kind of injury, previous contralateral hip fracture, length of stay, and peri-operative mortality did not differ significantly. In conclusion, a crude hip fracture incidence increase of about 50% in the northern Spanish region of Cantabria has taken place over the last 14 years. This effect does not persist after adjustments have been made for age. The crude rate increase occurred mainly at the expense of women, with a more noticeable rise in cervical fractures as opposed to trochanteric lesions.