Analysis of 16S rRNA Gene Sequence of Nasopharyngeal Exudate Reveals Changes in Key Microbial Communities Associated with Aging.

Functional or compositional perturbations of the microbiome can occur at different sites, of the body and this dysbiosis has been linked to various diseases. Changes in the nasopharyngeal microbiome are associated to patient's susceptibility to multiple viral infections, supporting the idea that the nasopharynx may be playing an important role in health and disease. Most studies on the nasopharyngeal microbiome have focused on a specific period in the lifespan, such as infancy or the old age, or have other limitations such as low sample size. Therefore, detailed studies analyzing the age- and sex-associated changes in the nasopharyngeal microbiome of healthy people across their whole life are essential to understand the relevance of the nasopharynx in the pathogenesis of multiple diseases, particularly viral infections. One hundred twenty nasopharyngeal samples from healthy subjects of all ages and both sexes were analyzed by 16S rRNA sequencing. Nasopharyngeal bacterial alpha diversity did not vary in any case between age or sex groups. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the predominant phyla in all the age groups, with several sex-associated. Acinetobacter, Brevundimonas, Dolosigranulum, Finegoldia, Haemophilus, Leptotrichia, Moraxella, Peptoniphilus, Pseudomonas, Rothia, and Staphylococcus were the only 11 bacterial genera that presented significant age-associated differences. Other bacterial genera such as Anaerococcus, Burkholderia, Campylobacter, Delftia, Prevotella, Neisseria, Propionibacterium, Streptococcus, Ralstonia, Sphingomonas, and Corynebacterium appeared in the population with a very high frequency, suggesting that their presence might be biologically relevant. Therefore, in contrast to other anatomical areas such as the gut, bacterial diversity in the nasopharynx of healthy subjects remains stable and resistant to perturbations throughout the whole life and in both sexes. Age-associated abundance changes were observed at phylum, family, and genus levels, as well as several sex-associated changes probably due to the different levels of sex hormones present in both sexes at certain ages. Our results provide a complete and valuable dataset that will be useful for future research aiming for studying the relationship between changes in the nasopharyngeal microbiome and susceptibility to or severity of multiple diseases.

Evaluation of PSA testing by general practitioners: regional study in the autonomic Community of Valencia.

OBJECTIVES: The aim of the study is to compare the use of PSA testing among general practitioners (GPs). METHODS: The number of PSA tests ordered by general practitioners in the years 2008-2009 was examined in a cross-sectional study of nine health districts of Spain. The percentage of PSA ordered to men younger than 50 (PSA<50/PSAtotal) and 40 years (PSA<40/PSAtotal) was calculated. The percentage of men over 50 years who were attended was also calculated and this data was compared with the number of PSA ordered to this population. For two of the departments, these data were also compared between GPs and urologists. RESULTS: PSA testing in 2009 is higher than 2008 in seven health districts. PSA testing in men younger than 50 years was increased along the period of the study and in men younger than 40 years remained steady. The differences between the values of the indicators for urologists and GPs are significant. CONCLUSIONS: The number of PSA tests and the percentage performed to men younger 50 years has been increasing and the variability is high. These data are suggestive for interventions focused on PSA testing and prostate cancer screening in primary care settings.

Did parental care in early life affect height? Evidence from rural Spain (19th-20th centuries).

This article examines the relationship between childhood mortality experienced within families and the height of surviving male children. Sibling mortality, controlled by different socioeconomic and environmental variables, is used as an approximation of the hygienic and epidemiological context and practices within the family. The analysis is based on a sample of 2783 individuals born between 1835 and 1977 in 14 villages in north-eastern Spain. The mortality data were obtained from the parish archives of the reference villages, and the height data from military service records of conscriptions at 21 years of age. The data were linked according to nominative criteria using family reconstitution methods. The results suggest the existence of a strong negative relationship between height and the childhood mortality experienced within families. Children born in families in which 50% of the children died before the age of five were up to 2.3 cm shorter than those of families with childhood mortality of less than 25%. General socioeconomic, hygienic and health improvements reduced childhood mortality, causing this link to gradually disappear between the 1940s and 1970s.

Pretarsal blepharospasm: Clinical and electromyographic characteristics.

OBJECTIVE: To describe the clinical and electromyographic characteristics of blepharospasm caused by selective involvement of the pars pretarsalis of the orbicularis oculi muscle. METHODS: Clinical assessment and simultaneous electromyographic recordings from levator palpebrae superioris and pars orbitaria and pretarsalis of orbicularis oculi muscles were performed in patients with blepharospasm and primary failure to botulinum toxin injections. Patients with selective abnormal electromyographic activity of the pars pretarsalis of the orbicularis oculi muscle were identified and treated with selective pretarsal injections of botulinum toxin. RESULTS: We found 24 patients with pretarsal blepharospasm confirmed by the electromyographic assessment. All of them were functionally blind. Three clinical-electromyographic patterns were identified: (a) Impairment of eyelid opening; (b) Increased blinking; (c) Spasms of eye closure combined with varying degrees of excessive blinking and impairment of eye-opening. Pretarsal injections of botulinum toxin induced a significant improvement in all patients and 50 % regained normal or near-normal vision. The clinical improvement was sustained after repeated pretarsal injections. CONCLUSIONS: Pretarsal blepharospasm can be suspected on clinical grounds and it can be confirmed by electromyographic recordings. SIGNIFICANCE: Recognition of this type of blepharospasm is important because of its excellent response to botulinum toxin injections applied into the pretarsal part of the orbicularis oculi muscle.

VALIDA project: Validation of allergy in vitro diagnostics assays (Tools and recommendations for the assessment of in vitro tests in the diagnosis of allergy).

In vitro allergen-specific immunoglobulin E (IgE) detection and quantification tests are routinely performed in clinical laboratories to diagnose patients with a suspected allergy. Numerous commercial assays are available to test for allergies, but the results can vary widely, thereby influencing both diagnosis and treatment. Given the challenges posed by differences in the various assays for in vitro determination of specific IgE, a group of experts has compiled in a document a series of recommendations on the implications that the use of a certain in vitro technique may have and the impact on the management of the allergic patient that the differences between the various techniques represent. The reading and analysis of this consensus document will help to understand the implications of the change of in vitro diagnostic method in the management of the patient with allergy, in the quality of life and in the socioeconomic costs associated with the disease.

Sonographic measurement of cross-sectional area of the median nerve in the diagnosis of carpal tunnel syndrome: correlation with nerve conduction studies.

PURPOSE: To assess the usefulness of sonographic measurement of the median nerve cross-sectional area (CSA) in the diagnosis of carpal tunnel syndrome (CTS) and grading of its severity using nerve conduction (NC) studies as the standard. METHOD: The CSA of the median nerve was measured at the tunnel inlet and outlet using the ellipse formula and automatic tracing in 72 hands with suspicion of CTS. RESULT: The lack of inter-reader reliability led to excluding CSA measurements obtained at the tunnel outlet. Based on the receiver operating characteristic curves, the following cut-off points for the CSA of the median nerve at the tunnel inlet was selected: 9.8 mm and 12.3 mm(2) for the ellipse formula and 11 and 13 mm(2) for automatic tracing. For the ellipse formula, a CSA less than or equal to 9.8 mm(2) excluded CTS whereas a CSA greater than or equal to 12.3 mm(2) was diagnostic of CTS with measurements between 9.8 and 12.3 mm(2) being indeterminate and requiring NC studies. For automatic tracing, the cutoff value of 11 mm(2) was excluded because of the high percentage of false negatives, whereas CSAs greater than or equal to 13 mm(2) were diagnostic of CTS. There were no statistically significant differences in CSA measurements between the various degrees of CTS severity determined by NC studies. CONCLUSION: Sonographic measurement of median nerve CSA at the tunnel inlet is a good alternative to NC studies as the initial diagnostic test for CTS, but it cannot grade the severity of CTS as well as NC studies.

A new optical density granulometry-based descriptor for the classification of prostate histological images using shallow and deep Gaussian processes.

BACKGROUND AND OBJECTIVE: Prostate cancer is one of the most common male tumors. The increasing use of whole slide digital scanners has led to an enormous interest in the application of machine learning techniques to histopathological image classification. Here we introduce a novel family of morphological descriptors which, extracted in the appropriate image space and combined with shallow and deep Gaussian process based classifiers, improves early prostate cancer diagnosis. METHOD: We decompose the acquired RGB image in its RGB and optical density hematoxylin and eosin components. Then, we define two novel granulometry-based descriptors which work in both, RGB and optical density, spaces but perform better when used on the latter. In this space they clearly encapsulate knowledge used by pathologists to identify cancer lesions. The obtained features become the inputs to shallow and deep Gaussian process classifiers which achieve an accurate prediction of cancer. RESULTS: We have used a real and unique dataset. The dataset is composed of 60 Whole Slide Images. For a five fold cross validation, shallow and deep Gaussian Processes obtain area under ROC curve values higher than 0.98. They outperform current state of the art patch based shallow classifiers and are very competitive to the best performing deep learning method. Models were also compared on 17 Whole Slide test Images using the FROC curve. With the cost of one false positive, the best performing method, the one layer Gaussian process, identifies 83.87% (sensitivity) of all annotated cancer in the Whole Slide Image. This result corroborates the quality of the extracted features, no more than a layer is needed to achieve excellent generalization results. CONCLUSION: Two new descriptors to extract morphological features from histological images have been proposed. They collect very relevant information for cancer detection. From these descriptors, shallow and deep Gaussian Processes are capable of extracting the complex structure of prostate histological images. The new space/descriptor/classifier paradigm outperforms state-of-art shallow classifiers. Furthermore, despite being much simpler, it is competitive to state-of-art CNN architectures both on the proposed SICAPv1 database and on an external database.

Serological study of Trypanosoma cruzi, Strongyloides stercoralis, HIV, human T cell lymphotropic virus (HTLV) and syphilis infections in asymptomatic Latin-American immigrants in Spain.

OBJECTIVE: We aimed to perform a serological screening for T. cruzi, Strongyloides stercoralis, HIV, human T cell lymphotropic virus (HTLV) and syphilis in Latin American immigrants admitted to hospital in Spain. METHODS: We have carried out a cross-sectional study of Latin American immigrants admitted to the Hospital General Universitario Alicante (Spain) from June 2012 to May 2014, where screening of Chagas disease, strongyloidiasis, HTLV, HIV and syphilis was performed by serology. RESULTS: A total 180 patients were included in the study. Patients' median age was 38 years old, 123 (68.3%; 123/180) were female and 57 (31.7%; 57/180) male. Five of the 180 (2.5%) patients were positive for Chagas disease; associated with knowledge about Chagas disease (p=0.005), previous contact with patients with Chagas disease (p=0.04) and being Bolivian (p<0.001). Forty-two of the 157 (26.8%) patients were positive for Strongyloides serology; associated positively with being male (p<0.001), eosinophilia (p=0.001), hyper-IgE (p<0.001) and being Ecuadorian (p=0.001), and negatively associated with being Colombian (p=0.03). Positive serology of latent syphilis was found in 1.8% (3/171) of patients. Serology of HTLV was negative in all cases. No new cases of HIV infection were diagnosed. CONCLUSIONS: We propose that Latin American immigrant patients admitted to hospital in Spain be screened for strongyloidiasis, Chagas disease and syphilis by serology.

Acute effects of dipyrone on renal function in patients with cirrhosis: a randomized controlled trial.

Use of non-steroidal anti-inflammatory drugs in cirrhosis has been associated with impairment of renal function based on its ability to inhibit the renal production of prostaglandins. Renal effects of dipyrone in patients with cirrhosis have not been evaluated. We aimed to assess the renal effect of therapeutic doses of dipyrone used for short periods of time in patients with cirrhosis. Twenty-nine patients with cirrhosis were included in an observer-blind clinical trial. Patients were randomized to receive three times a day oral acetaminophen (500 mg; N = 15) or dipyrone (575 mg; N = 14) for 72 hr. Serum and urine samples were obtained at baseline, 48 and 72 hr, and cystatin C, creatinine, aldosterone, 6-keto-Prostaglandin-F1 alpha and prostaglandin E2 were measured. Cystatin C and creatinine levels remained comparable in patients treated with acetaminophen and dipyrone. Urine and serum prostaglandins concentrations were significantly decreased at 72 hr in patients treated with dipyrone regardless of the status of ascites. One patient with ascites treated with dipyrone required a paracentesis and developed renal insufficiency. We conclude that dipyrone and acetaminophen did not reduce renal function when used for short periods of time (up to 72 hr) in patients with cirrhosis. However, considering that dipyrone lowered renal vasodilator prostaglandins synthesis, acetaminophen appears as the safest choice with respect to kidney function in cirrhosis.

Effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity at 28 days in critically ill patients with systemic inflammatory response syndrome: a randomized, single-blind, prospective, multicenter study.

We investigated the effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity and mortality in critically ill patients who developed systemic inflammatory response syndrome after an acute event. Eleven intensive care units in tertiary-care hospitals participated in a prospective, randomized, single blind, multicenter trial. Eighty-four patients with systemic inflammatory response syndrome of any etiology were randomly allocated to receive a glutamine-enriched enteral diet or a control diet without glutamine.Most patients received the planned caloric intake. The number of infected patients was smaller in the glutamine group than in the control group (11 versus 17 patients, P < 0.05), with a relative risk of 0.5 (95% confidence interval = 0.3-0.9). The most frequent infection was nosocomial pneumonia, with 11 (33%) patients in the control group and 6 (14%) in the glutamine group. There were no differences with respect to other infections, mortality, or length of stay. Intestinal permeability as assessed by the lactulose-mannitol test was unchanged in both groups.Glutamine-enriched enteral diets can decrease nosocomial infections in patients with systemic inflammatory response syndrome.

Eyelid movements in health and disease. The supranuclear impairment of the palpebral motility.

The eyelid movements are mediated mainly by the orbicularis oculi (OO) and the levator palpebrae superioris (LPS) muscles. Dissociated upper lid functions exhibit different counterbalanced action of these muscles, and in blinking they show a strictly reciprocal innervation. The disturbance of this close LPS-OO relationship likely leads to many of the central lid movement disorders. Three groups of supranuclear motor impairment of lid movements are considered: the disorders of the lid-eye movements' coordination, the disturbances of blinking and lid "postural" maintenance, and the alteration of voluntary lid movements. Nuclei of the posterior commissure control the inhibitory modulation of LPS motor-neuronal activity and they are involved in the lid-eye coordination disorders such as lid retraction, which is observed in the Parinaud's syndrome and also in parkinsonism and progressive supranuclear palsy. Spontaneous (SB) and reflex blinking consist of two components: the inhibition of the basal tonic LPS activity, which keeps the eyes open, and the concurrent activation of the OO muscles. LPS inhibition precedes and outlasts the OO activation. This normal configuration is impaired in parkinsonism and blepharospasm (BSP). SB shows a highly interindividual rate variation (among 10-20 per minute in adults) and abnormal blink rates occur in neurological diseases related to dopaminergic transmission impairments. Lid postural abnormalities include involuntary eyelid closure, which is usually associated with inability to open the eyes. Two major disorders share these two aspects: BSP and blepharocolysis (BCO). BSP consists of an involuntary overactivity of the OO, with LPS co-contraction activity, and is expressed as frequent and prolonged blinks, clonic bursts, prolonged tonic contraction or a blend of all of them. BCO (commonly named "so-called lid opening apraxia") is an overinhibition of the LPS with no evidence of ongoing OO activity. BSP and BCO occur in many instances of idiopathic dystonias and basal ganglia diseases and, less frequently, in rostral brainstem lesions. Both may coincide in the same patient. Voluntary lid movement disorders comprise the impairment of Bell's phenomenon, the voluntary eyelid closure palsy and the so-called cerebral ptosis, all related to lesions of frontal cortical areas and/or the corticospinal system.

Intestinal permeability is increased in patients with advanced cirrhosis.

BACKGROUND/AIMS: The dysfunction of the intestinal barrier is a factor that has been related to bacterial translocation from lumen to extra-intestinal sites and consequently to the development of spontaneous bacterial peritonitis. The aim of this study was to investigate if the alterations of the intestinal barrier in cirrhosis are related with the degree of liver failure and associated with other clinical complications. METHODOLOGY: Intestinal permeability was assessed by means of the lactulose/mannitol test in 79 cirrhotic and 25 controls subjects. They received 10 g of lactulose and 5 g of mannitol. Lactulose and mannitol were measured in a five-hour urinary volume. RESULTS: Lactulose/mannitol ratio was significantly higher in cirrhotic patients than in controls (p = 0.03). This was more evident in end-stage cirrhosis. Patients with ascites, or encephalopathy showed a statistically significant increase in lactulose/mannitol ratio when compared to patients without these complications. CONCLUSIONS: The increased intestinal permeability is related to the progression of the liver disease and is more relevant with overt clinical complications. This is due to an increased absorption of lactulose. However, as liver disease progresses, mannitol absorption is progressively reduced, probably due to a reduced surface of absorption, and these events are more relevant in patients with overt clinical complications.

[Prognostic value of serum levels of tumor necrosis factor-alpha in patients with heart failure]. / Valor pronóstico de los niveles séricos del factor de necrosis tumoral alfa en pacientes con insuficiencia cardíaca.

INTRODUCTION AND OBJECTIVE: Tumor necrosis factor-alpha is an inflammatory cytokine which rises in heart failure and has prognostic value in severe cases. Its value is less established in moderate cases. Our aim was to determine its prognostic value in cases from a community hospital. PATIENTS: We studied 50 patients, average age 59.5 12.3 years, with dilated cardiomyopathy (72% non-ischemic) and moderate heart failure (59% functional class II). METHODS: Patients were evaluated with an echocardiogram and cardiopulmonary treadmill stress test (Naughton), muscular strength measurements (hand dynamometer), blood tumor necrosis factor levels, and an average follow-up of 17.5 9 months (range, 1-29 months). All causes of mortality, cardiac transplantation, and readmissions for heart failure were recorded. RESULTS: Twenty-three patients experienced events. These patients were older (63 +/- 12.7 vs 55.7 +/- 11.4 years; p = 0.042), had a lower peak VO2 (13.7 +/- 3.9 vs 16 +/- 3.3 ml/kg/min; p = 0.035), and higher peak VE/VCO2 and factor levels [41.9 +/- 10.6 vs 33.2 +/- 5.7; p = 0.001 and 4.3 (3.1-7.9) vs 3.3 (2.4-4.3) pg/ml; p = 0.021, respectively]. In the Cox model, the only variable with independent prognostic value was peak VE/VCO2 [HR 1.13 (1.07-1.19); p < 0.001]. The best cutoff point was 34.5 (sensitivity, 86.4%; specificity, 58.3%; p = 0.0007). The cytokine had no independent prognostic value. CONCLUSIONS: Our patients with events were older, had a lower peak VO2, and higher peak VE/VCO2 and serum tumor necrosis factor levels. However, only peak VE/VCO2 had independent prognostic value.

Merging person-specific bio-markers for predicting oral cancer recurrence through an ontology.

One of the major problems related to cancer treatment is its recurrence. Without knowing in advance how likely the cancer will relapse, clinical practice usually recommends adjuvant treatments that have strong side effects. A way to optimize treatments is to predict the recurrence probability by analyzing a set of bio-markers. The NeoMark European project has identified a set of preliminary bio-markers for the case of oral cancer by collecting a large series of data from genomic, imaging, and clinical evidence. This heterogeneous set of data needs a proper representation in order to be stored, computed, and communicated efficiently. Ontologies are often considered the proper mean to integrate biomedical data, for their high level of formality and for the need of interoperable, universally accepted models. This paper presents the NeoMark system and how an ontology has been designed to integrate all its heterogeneous data. The system has been validated in a pilot in which data will populate the ontology and will be made public for further research.

[An evaluation of glycosylated hemoglobin requesting patterns in a primary care setting: a pilot experience in the Valencian Community (Spain)]. / Evaluación del patrón de solicitud de hemoglobina glucosilada por Atención Primaria: estudio piloto regional en la Comunidad Valenciana.

OBJECTIVE: To assess the pattern of glycosylated hemoglobin (HbA(1c)) requests by clinicians from eight health departments by calculating indicators of demand appropriateness. METHODS: A cross-sectional study of the number of HbA(1c) requests by primary care clinics in 2008 and 2009. The indicator of demand appropriateness was the proportion of HbA(1c) values lower than 6.5%. Variables were collected and indicators were automatically calculated. The number of HbA(1c) measurements that should theoretically have been requested according to known diabetes prevalence data was also calculated. RESULTS: A progressive increase was seen in demand for HbA(1c) measurements. Approximately 54% of HbA(1c) values obtained in seven of the eight departments studied were lower than 6.5%. The number of theoretical HbA(1c) requests that would have been expected based on the known prevalence of diabetes was higher than the number of HbA(1c) requests in all departments. CONCLUSION: The results appear to suggest that HbA(1c) requests by the health departments studied were not always appropriate. HbA(1c) measurements were probably overused in patients without diabetes and underused in patients with diabetes.

Regional variations in test requiring patterns of general practitioners in Spain.

OBJECTIVE: To analyze the requesting patterns for a range of laboratory tests ordered in 2009 from eight laboratories providing services to eight health areas, using appropriate indicators. DESIGN: Indicators measured every test request per 1,000 inhabitants, and indicators that measured the number of tests per related test requested by general practitioners were calculated. The savings generated, if each Health Care Department achieved the appropriate indicator standard, were also calculated. Laboratory Information System registers were collected, and indicators were calculated automatically in each laboratory using a data warehouse application. RESULTS: There was a large difference in demand for tests by health areas. The ratio of related tests also showed a great variability. The savings generated if each Health Care Department had achieved the appropriate indicator standard were €172,116 for free thyroxine, €18,289 for aspartate aminotransferase, and €62,678 for urea. CONCLUSIONS: Considerable variability exists in general practitioners' demand for laboratory tests.

[Critical illness myopathy. Neurophysiological and muscular biopsy assessment in 33 patients]. / Miopatia del enfermo crítico. Valoracion neurofisiológica y biopsia muscular en 33 pacientes.

INTRODUCTION: Critical illness patients may show marked weakness acquired in the Intensive Care Unit (ICU). There are some disagreements about the myopathic versus neuropathic damage in this condition, presumably due to the lack of reliable diagnostic criteria. AIMS: To report the neurophysiological findings in critical patients, to classify them in groups according to the electro-physiological data of myopathy, and to ascertain the rapport between the neurophysiological classification of myopathy and the muscle biopsy results. PATIENTS AND METHODS: A prospective assessment of 33 ICU patients with marked weakness by means of needle electro-myography, electroneurography, and percutaneous muscle biopsy was carried out. Direct muscle stimulation was performed in 9 patients and repetitive nerve stimulation in 14 cases. RESULTS. According to neurophysiological criteria, patients were classified in 3 groups: definite (33%), probable (46%), and uncertain (21%) myopathy. The most conspicuous myopathic pathological findings including fibrillar atrophy and necrosis, vacuoles, and myosin and mitochondrial anomalies, were observed in both, definite and probable groups (26 patients). In 17 of these cases, low amplitude of the compound motor action potentials and normal sensory nerve action potentials were found. Axonal sensory-motor neuropathy was present in 11 patients, concomitant with neurophysiological data of myopathy in 7 cases. CONCLUSIONS: Based on the neurophysiological criteria for the assessment and classification of acquired weakness in critically ill patients, myopathy is highly predominant over the neuropathic impairment. Histopathological findings are closely related to the electrophysiological diagnosis of myopathy. Neither neurophysiological nor pathological data support a hypothetic motor axonal neuropathy in this series.

Experimental and DFT studies on the transmission mechanisms of analogous NMR JCH and JCC couplings in 1-X- and 1-X-3-methylbicyclo[1.1.1]-pentanes.

The main aim of this work is to compare the transmission mechanisms for the Fermi contact term of spin-spin couplings, SSCCs, in series 1-X-bicyclo[1.1.1]-pentane, (1), and 1-X-3-methylbicyclo[1.1.1]pentane, (2), and from that comparison to gain insight into some subtle aspects of the FC transmission. To this end, 18 members of the latter series were isotopically enriched in (13)C at the methyl position and the following couplings were measured; 1JC3CMe, 3JC1CMe and 4JCXCMe. These three types of SSCCs in (2) are compared, respectively, with 1JC3H3, 3JC1H3 and 4JCXH in (1); these latter values were taken from previous works. Since electron delocalization plays an important role in the transmission of the FC interaction, the natural bond orbital (NBO) method is employed to quantify electron delocalization interactions within selected members of series (1) and (2). It is found that 1JC3H3 SSCCs in (1) is more efficiently transmitted than 1JC3CMe SSCCs in (2). On the other hand, 3JC1H3 and 4JCXH SSCCs in (1) are notably less efficiently transmitted than 3JC1CMe and 4JCXCMe SSCCs in (2), although substituent effects on these two SSCCs show the opposite trends. These different efficiencies are rationalized in terms of different sigma-hyperconjugative interactions in both series of compounds.

Experimental and theoretical study of hyperconjugative interaction effects on NMR 1J(CH) scalar couplings.

Hyperconjugative and electrostatic interactions effects on 1J(CH) spin-spin coupling constants (SSCCs) are critically studied from both theoretical and experimental points of view. A qualitative model is used to predict how the former affect such SSCCs, while electrostatic interactions are modeled with a point charge placed in the vicinity of the corresponding sigma(CH) bond. Hyperconjugative interactions are calculated using the "natural bond orbital" approach, and using the point-charge model, it is shown how intertwined are both types of interactions. Several members of the series 1-X-bicyclo[1.1.1]pentane and 1-X-3-methylbicyclo[1.1.1]pentane are chosen as model compounds for measuring 1J(CH) SSCCs; in some of them were performed also DFT-SSCC calculations. The strained cage substrate in these series defines strong sigma-hyperconjugative interactions, making these compounds excellent examples to verify the qualitative model presented in this work. It is verified that (a) hyperconjugative interactions from the sigma(CH) bond or into the sigma(CH) antibond containing the coupling nuclei yield a decrease of the corresponding 1J(CH) SSCC and (b) hyperconjugative interactions from other bonds involving the coupling C nucleus yield an increase of that 1J(CH) SSCC.