Increased variance in second electrode accuracy during deep brain stimulation and its relationship to pneumocephalus, brain shift, and clinical outcomes: A retrospective cohort study.

•Overall electrode accuracy was 0.22+/-0.4 â€‹mm with only 3 (4%) electrodes out with 2 â€‹mm from the intended target.•Accuracy was significantly worse in the GPi versus the STN and on the second side implanted.•Inaccuracy occurred in the X (lateral) plane but was not related to pneumocephalus or brain shift.

Suicide intervention training with law enforcement officers.

Law Enforcement Officers' (LEO) interactions with people facing mental health crises have risen exponentially since the era of deinstitutionalization. On average, about 10% of the individuals law enforcement interacts with daily have mental health challenges. Several factors influence the outcome of these interactions, not least of which is an officer's role as a gatekeeper as well as their training related to people with mental health challenges. We hypothesized that participating in the online QPR Training for Law Enforcement Officers would be associated with improved knowledge about suicide, attitudes to suicide and suicide intervention, and self-efficacy. Additionally, we hypothesized that these outcomes would be associated with greater use of intervention skills when encountering individuals at risk for suicide in the community. Results of our longitudinal analysis find that most of the participating officers reported some prior training and yet demonstrated statistically significant improvements in knowledge and attitudes after controlling for previous training. No significant changes were observed in LEO's use of intervention skills following training. We conclude by suggesting that there is substantial need for increased training; and offering possible conceptual and empirical explanations for the observed results.

Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet.

BACKGROUND: The contemporary American diet figures centrally in the pathogenesis of numerous chronic diseases-'diseases of civilization'. We investigated in humans whether a diet similar to that consumed by our preagricultural hunter-gatherer ancestors (that is, a paleolithic type diet) confers health benefits. METHODS: We performed an outpatient, metabolically controlled study, in nine nonobese sedentary healthy volunteers, ensuring no weight loss by daily weight. We compared the findings when the participants consumed their usual diet with those when they consumed a paleolithic type diet. The participants consumed their usual diet for 3 days, three ramp-up diets of increasing potassium and fiber for 7 days, then a paleolithic type diet comprising lean meat, fruits, vegetables and nuts, and excluding nonpaleolithic type foods, such as cereal grains, dairy or legumes, for 10 days. Outcomes included arterial blood pressure (BP); 24-h urine sodium and potassium excretion; plasma glucose and insulin areas under the curve (AUC) during a 2 h oral glucose tolerance test (OGTT); insulin sensitivity; plasma lipid concentrations; and brachial artery reactivity in response to ischemia. RESULTS: Compared with the baseline (usual) diet, we observed (a) significant reductions in BP associated with improved arterial distensibility (-3.1+/-2.9, P=0.01 and +0.19+/-0.23, P=0.05);(b) significant reduction in plasma insulin vs time AUC, during the OGTT (P=0.006); and (c) large significant reductions in total cholesterol, low-density lipoproteins (LDL) and triglycerides (-0.8+/-0.6 (P=0.007), -0.7+/-0.5 (P=0.003) and -0.3+/-0.3 (P=0.01) mmol/l respectively). In all these measured variables, either eight or all nine participants had identical directional responses when switched to paleolithic type diet, that is, near consistently improved status of circulatory, carbohydrate and lipid metabolism/physiology. CONCLUSIONS: Even short-term consumption of a paleolithic type diet improves BP and glucose tolerance, decreases insulin secretion, increases insulin sensitivity and improves lipid profiles without weight loss in healthy sedentary humans.

A practical approach to the balance between acid production and renal acid excretion in humans.

Precise measurements of net endogenous acid production (NEAP) to determine net acid balance require labor and laboratory intensive steady-state measurements of dietary nutrient intakes and urine and stool composition. In an effort to simplify the task, investigators have devised several alternative methodologies, especially computational predictive models based on diet composition. This paper describes the so-called gold standard, and the details of each alternative methodology, discussing their strengths and potential pitfalls. We also briefly discuss what we believe the optimal NEAP for adult humans, and how to achieve that through diet.

Queuosine modification of tRNA: a case for convergent evolution.

Queuosine is a hypermodified nucleoside found in position 34, the anticodon wobble position, of four tRNA species. This modification is distributed with near uniformity across all life forms found on this planet. Yet the molecular mechanisms involved with accomplishing this ubiquitous posttranscriptional modification of tRNA are dramatically different between prokaryotic and eukaryotic organisms, which suggests that these were formed by convergent evolution of a fundamental life process essential to nearly all life forms. This minireview describes the differences between these modification systems and points to a new direction for developing research on the molecular function queuosine-modified tRNA in diverse species.

Chloride-sensitive renal microangiopathy in the stroke-prone spontaneously hypertensive rat.

BACKGROUND: In the stroke-prone spontaneously hypertensive rat (SHRSP) fed a low-normal NaCl diet, we recently reported that supplemental KCl, but not KHCO(3) or K-citrate (KB/C), exacerbated hypertension and induced hyperreninemia and strokes. We now ask the following question: In these SHRSP, is either such selectively Cl(-)-sensitive hypertension or hyperreninemia a pathogenetic determinant of renal microvasculopathy? METHODS: SHRSPs were randomized to either supplemental KCl, KB/C, or nothing (control) at 10 weeks of age. Four and 14 weeks afterward, we assessed renal microangiopathy histologically and measured plasma renin activity (PRA). From randomization, blood pressure was measured radiotelemetrically and continually; proteinuria was measured periodically. RESULTS: KCl, but not KB/C, amplified renal microangiopathy and proteinuria. Four weeks after randomization, when KCl initially exacerbated hypertension, renal microangiopathy, hyperproteinuria, and hyperreninemia had not yet occurred. However, across all groups, the increment of SBP at four weeks strongly predicted its final increment, severity of renal microangiopathy, proteinuria, and PRA 14 weeks after randomization. Then, the severity of renal microangiopathy varied directly with the levels of systolic blood pressure (SBP; R(2) = 0.9, P < 0.0001), PRA (R(2) = 0.7, P < 0.0001), and proteinuria (R(2) = 0.8, P < 0.0001) as continuous functions across all treatment groups. Renal creatinine clearance was greater with KB/C. CONCLUSIONS: In the SHRSP, (1) like cerebral microangiopathy, renal microangiopathy is selectively Cl(-) sensitive and hence, systemic microangiopathy is as well; (2) Cl(-) likely amplifies microangiopathy by exacerbating hypertension and possibly also by increasing PRA; and (3) Cl(-) might increase blood pressure and PRA by further constricting the renal afferent arteriole.

Online tables of contents for books: effect on usage.

OBJECTIVES: To explore whether the presence of online tables of contents (TOC) in an online catalog affects circulation (checkouts and inhouse usage). Two major questions were posed: (1) did the presence of online tables of contents for books increase use, and, (2) if it did, what factors might cause the increase? METHOD: A randomized and stratified design was used in tracking usage of 3,957 book titles that were previously divided into two groups: one with TOC and one without TOC. Stratification was done for year of imprint, location, subject, previous use, circulating or non-circulating status, and presence of TOC. The use was tracked by the online catalog statistics in the InnoPac online catalog for fourteen months. RESULTS: The study found that tables of contents do increase usage. It also showed a correlation in the size of the effect based on the currency of the titles. In general, even after adjusting for all of the variables (publication date, location, circulation status, subject, and previous use), the odds of a title being used increased by 45% if the titles had online tables of contents, a statistically significant impact at the 0.05 level. CONCLUSIONS: This case-control study presents new information about the impact on circulation and inhouse use when tables of contents for books are added to the online catalog record. The study helps to establish the positive role of tables of contents in online catalogs. The research establishes TOC as a major parameter that can be successfully studied using quantitative methods. The study also provides information professionals with some guidance on when enhancement of TOC is likely to be most effective in increasing the use of existing collections.

Diet, evolution and aging--the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet.

Theoretically, we humans should be better adapted physiologically to the diet our ancestors were exposed to during millions of years of hominid evolution than to the diet we have been eating since the agricultural revolution a mere 10,000 years ago, and since industrialization only 200 years ago. Among the many health problems resulting from this mismatch between our genetically determined nutritional requirements and our current diet, some might be a consequence in part of the deficiency of potassium alkali salts (K-base), which are amply present in the plant foods that our ancestors ate in abundance, and the exchange of those salts for sodium chloride (NaCl), which has been incorporated copiously into the contemporary diet, which at the same time is meager in K-base-rich plant foods. Deficiency of K-base in the diet increases the net systemic acid load imposed by the diet. We know that clinically-recognized chronic metabolic acidosis has deleterious effects on the body, including growth retardation in children, decreased muscle and bone mass in adults, and kidney stone formation, and that correction of acidosis can ameliorate those conditions. Is it possible that a lifetime of eating diets that deliver evolutionarily superphysiologic loads of acid to the body contribute to the decrease in bone and muscle mass, and growth hormone secretion, which occur normally with age? That is, are contemporary humans suffering from the consequences of chronic, diet-induced low-grade systemic metabolic acidosis? Our group has shown that contemporary net acid-producing diets do indeed characteristically produce a low-grade systemic metabolic acidosis in otherwise healthy adult subjects, and that the degree of acidosis increases with age, in relation to the normally occurring age-related decline in renal functional capacity. We also found that neutralization of the diet net acid load with dietary supplements of potassium bicarbonate (KHCO3) improved calcium and phosphorus balances, reduced bone resorption rates, improved nitrogen balance, and mitigated the normally occurring age-related decline in growth hormone secretion--all without restricting dietary NaCl. Moreover, we found that co-administration of an alkalinizing salt of potassium (potassium citrate) with NaCl prevented NaCl from increasing urinary calcium excretion and bone resorption, as occurred with NaCl administration alone. Earlier studies estimated dietary acid load from the amount of animal protein in the diet, inasmuch as protein metabolism yields sulfuric acid as an end-product. In cross-cultural epidemiologic studies, Abelow found that hip fracture incidence in older women correlated with animal protein intake, and they suggested a causal relation to the acid load from protein. Those studies did not consider the effect of potential sources of base in the diet. We considered that estimating the net acid load of the diet (i. e., acid minus base) would require considering also the intake of plant foods, many of which are rich sources of K-base, or more precisely base precursors, substances like organic anions that the body metabolizes to bicarbonate. In following up the findings of Abelow et al., we found that plant food intake tended to be protective against hip fracture, and that hip fracture incidence among countries correlated inversely with the ratio of plant-to-animal food intake. These findings were confirmed in a more homogeneous population of white elderly women residents of the U.S. These findings support affirmative answers to the questions we asked above. Can we provide dietary guidelines for controlling dietary net acid loads to minimize or eliminate diet-induced and age-amplified chronic low-grade metabolic acidosis and its pathophysiological sequelae. We discuss the use of algorithms to predict the diet net acid and provide nutritionists and clinicians with relatively simple and reliable methods for determining and controlling the net acid load of the diet. A more difficult question is what level of acidosis is acceptable. We argue that any level of acidosis may be unacceptable from an evolutionarily perspective, and indeed, that a low-grade metabolic alkalosis may be the optimal acid-base state for humans.

Worldwide incidence of hip fracture in elderly women: relation to consumption of animal and vegetable foods.

BACKGROUND: Hip fracture, a major health problem in elderly persons, varies in incidence among the populations of different countries and is directly related to animal protein intake, a finding that suggests that bone integrity is compromised by endogenous acid production consequent to the metabolism of animal proteins. If that is so, vegetable foods might provide a countervailing effect, because they are a rich source of base (bicarbonate) in the form of metabolizable organic anions, which can neutralize protein-derived acid and supply substrate (carbonate) for bone formation. METHODS: We analyzed reported hip fracture incidence (HFI) data among countries (N = 33) in women aged 50 years and older, in relation to corresponding country-specific data on per capita consumption of vegetable and animal foods as reported by the United Nations Food and Agriculture Organization. RESULTS: HFI varied directly with total (r = +.67, p < .001) and animal (r = +.82, p < .001) protein intake and inversely with vegetable protein intake (r = .37, p < .04). The countries in the lowest tertile of HFI (n = 11) had the lowest animal protein consumption, and invariably, vegetable protein (VP) consumption exceeded the country's corresponding intake of animal protein (AP): VP/AP > 1.0. By contrast, among the countries in the highest tertile of HFI, animal protein intake exceeded vegetable protein intake in nearly every case (10 of 11 countries). Among all countries, HFI correlated inversely and exponentially with the ratio of vegetable/animal protein intake (r = -.84, p < .001) and accounted for 70% of the total variation in HFI. Adjusted for total protein intake, vegetable food consumption was an independent negative predictor of HFI. All findings were similar for the subset of 23 countries whose populations are predominantly Caucasian. CONCLUSION: The findings suggest that the critical determinant of hip fracture risk in relation to the acid-base effects of diet is the net load of acid in the diet, when the intake of both acid and base precursors is considered. Moderation of animal food consumption and an increased ratio of vegetable/animal food consumption may confer a protective effect.

Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion.

BACKGROUND: The chronic low-grade metabolic acidosis that occurs in various renal disorders and in normal people, and that is related both to dietary net acid load and age-related renal functional decline, may contribute to osteoporosis by increasing urine calcium excretion. Administration of potassium (K) alkali salts neutralizes acid and lowers urine calcium excretion. Urine calcium excretion also can be reduced by the administration of thiazide diuretics, which are often given with supplemental K to avoid hypokalemia. We determined whether the K alkali salt potassium bicarbonate (KHCO3) and the thiazide diuretic hydrochlorothiazide (HCTZ) combined is more effective in reducing urinary calcium than KHCO3 alone or HCTZ combined with the conventionally coadministered nonalkalinizing K salt potassium chloride (KCl). METHODS: Thirty-one healthy men and women aged 50 or greater were recruited for a four-week, double-blind, randomized study. After a baseline period of 10 days with three 24-hour urine and arterialized blood collections, subjects were randomized to receive either HCTZ (50 mg) plus potassium (60 mmol daily) as either the chloride or bicarbonate salt. Another 19 women received potassium bicarbonate (60 mmol) alone. After two weeks, triplicate collections of 24-hour urines and arterialized bloods were repeated. RESULTS: Urinary calcium excretion decreased significantly in all groups. KHCO3 alone and HCTZ + KCl induced similar decreases (-0.70 +/- 0.60 vs. -0.80 +/- 1. 0 mmol/day, respectively). Compared with those treatments, the combination of HCTZ + KHCO3 induced more than a twofold greater decrease in urinary calcium excretion (-1.8 +/- 1.2 mmol/day, P < 0. 05). Both HCTZ + KHCO3 and KHCO3 alone reduced net acid excretion significantly (P < 0.05) to values of less than zero. CONCLUSIONS: KHCO3 was superior to KCl as an adjunct to HCTZ, inducing a twofold greater reduction in urine calcium excretion, and completely neutralizing endogenous acid production so as to correct the pre-existing mild metabolic acidosis that an acid-producing diet usually induces in older people. Accordingly, for reducing urine calcium excretion in stone disease and osteoporosis, the combination of HCTZ + KHCO3 may be preferable to that of HCTZ + KCl.

Serious fireworks-related eye injuries.

OBJECTIVE: To analyze and compare epidemiological and clinical information on serious fireworks-related eye injuries from two affiliates of the United States Eye Injury Registry. METHOD: Retrospective review. RESULTS: In the Eye Injury Registry of Alabama (EIRA) database, 185 of the 4150 injuries (4.4%) were caused by fireworks. In the Hungarian Eye Injury Registry database, only two of the 1245 cases (0.1%, p=0.000001) were fireworks-related. In the EIRA, 79% of patients were males and 87% were under 31 years. A bystander was injured in 67% of the cases, being an average of 23 feet away; 39% of bystanders had a final vision < or =19/200. No injured person wore eye protection. Bottle rockets caused 80% of the 185 injuries. Overall, 20% of eyes had <5/200 final visual acuity. Twenty-five percent of bottle rocket-injured eyes, compared to 64% of those injured by other devices, had > or =20/40 final vision (p=0. 000004). CONCLUSIONS. The rate of fireworks-related serious eye injuries has not decreased in Alabama in the last 16 years; most patients are young males. Since bystanders are at a measurable risk even at a distance of 100 feet, wearing eye protection is recommended to both bystanders and operators. Bottle rockets cause most of the injuries and the more severe ones, and should be the prime target for prevention. The benefit of a strict and enforced legislative ban on private fireworks displays is demonstrated by the much lower incidence figure in Hungary. Such a ban should be considered in other countries where fireworks-related eye injuries are common.

Differing effects of supplemental KCl and KHCO3: pathophysiological and clinical implications.

Compared to the prehistoric diet, the modern human diet contains not only excessive NaCl and deficient K+, but also deficient precursors of HCO3- and sometimes excessive precursors of nonvolatile acid. The mismatch between the modern diet and the still ancient biological machinery of humans subtly but chronically disorders their internal milieu, giving rise to a prolonged state of low-grade potassium deficiency and low-grade metabolic acidosis whose severity increases with age. Supplemental KCI cannot redress this mismatch and correct this state. However, the mismatch is redressed and the state corrected by restoring intakes of K+ and HCO3- to levels approaching those in the diet of our prehistoric forebearers, with either fruits and vegetables or with supplemental KHCO3. So restored, KHCO3 can: 1) attenuate hypertension and possibly prevent its occurrence by suppressing the phenomenon of normotensive NaCl-sensitivity, in part by its natriuretic effect; (2) prevent kidney stones by reducing urinary excretion of calcium and increasing urinary excretion of citrate; (3) ameliorate and protect against the occurrence of osteoporosis by increasing the renal retention of calcium and phosphorus, and by suppressing bone resorption and enhancing bone formation; and (4) likely prevent stroke.

Determination of queuosine modification system deficiencies in cultured human cells.

Queuosine-deficient tRNAs are often observed in neoplastic cells. In order to determine possible sites for malfunction of the multistep queuosine modification system, comprehensive studies were performed on two human neoplastic cell lines, the HxGC(3) colon adenocarcinoma and the MCF-7 breast adenocarcinoma, which are 100 and 50-60% queuosine deficient, respectively. These results were compared with data obtained from normal human fibroblast (HFF) cultures which maintain 100% queuosine-modified tRNA populations. Queuine uptake in all three cell types was similar and each demonstrated activation by protein kinase C (PKC). However, incorporation of queuine into tRNA by tRNA:guanine ribosyltransferase (TGRase; E.C. 2.4.2.24) and PKC-catalyzed activation of this enzyme occurred only in HFF and MCF-7 cells. The HxGC(3) cell line exhibited no TGRase activity as was expected. Treatment with 5-azacytidine (5-azaC) induced TGRase activity to a level 20% of that in HFF and MCF-7 cells; however, this 5-azaC-induced TGRase activity was not regulated by PKC. Salvage of the queuine base from tRNA degradation products has been shown in mammalian cells and was measured in the HFF cells. However, salvage activity in the MCF-7 cell line was deficient. Therefore, it was shown by direct measurements that the HxGC(3) cell line is completely lacking in queuosine-modified tRNA due to loss of functional TGRase, while the MCF-7 cell line has an inefficient queuine salvage mechanism resulting in a significant deficiency of queuosine-modified tRNA. These techniques can be applied to any cultured cell types to determine specific lesions of the queuosine modification system, which have been suggested to be associated with neoplastic progression.

The effect of queuosine on tRNA structure and function.

Computational modeling was performed to determine the potential function of the queuosine modification of tRNA found in wobble position 34 of tRNAasp, tRNAasn, tRNAhis, and tRNAtyr. Using the crystal structure of tRNAasp and a tRNA-tRNA-mRNA complex model, we show that the queuosine modification serves as a structurally restrictive base for tRNA anticodon loop flexibility. An extended intraresidue and intramolecular hydrogen bonding network is established by queuosine. The quaternary amine of the 7-aminomethyl side chain hydrogen bonds with the base's carbonyl oxygen. This positions the dihydroxycyclopentenediol ring of queuosine in proper orientation for hydrogen bonding with the backbone of the neighboring uridine 33 residue. The interresidue association stabilizes the formation of a cross-loop hydrogen bond between the uridine 33 base and the phosphoribosyl backbone of the cytosine at position 36. Additional interactions between RNAs in the translation complex were studied with regard to potential codon context and codon bias effects. Neither steric nor electrostatic interaction occurs between aminoacyl- and peptidyl-site tRNA anticodon loops that are modified with queuosine. However, there is a difference in the strength of anticodon/codon associations (codon bias) based on the presence or lack of queuosine in the wobble position of the tRNA. Unmodified (guanosine-containing) tRNAasp forms a very stable association with cytosine (GAC), but is much less stable in complex with a uridine-containing codon (GAU). Queuosine-modified tRNAasp exhibits no bias for either of cognate codons GAC or GAU and demonstrates a lower binding energy similar to the wobble pairing of guanosine-containing tRNA with a GAU codon. This is proposed to be due to the inflexibility of the queuosine-modified anticodon loop to accommodate proper positioning for optimal Watson-Crick type associations. A preliminary survey of codon usage patterns in oncodevelopmental versus housekeeping gene transcripts suggests a significant difference in bias for the queuosine-associated codons. Therefore, the queuosine modification may have the potential to influence cellular growth and differentiation by codon bias-based regulation of protein synthesis for discrete mRNA transcripts.

Normotensive salt sensitivity: effects of race and dietary potassium.

-Normotensive salt sensitivity, a putative precursor of hypertension, might be quite frequent in African Americans (blacks) and less frequent in Caucasian Americans (whites), but only when dietary potassium is deficient and not when maintained well within the normal range. We tested this hypothesis in 41 metabolically controlled studies of 38 healthy normotensive men (24 blacks, 14 whites) who ate a basal diet low in sodium (15 mmol/d) and marginally deficient in potassium (30 mmol/d) for 6 weeks. Throughout the last 4 weeks, NaCl was loaded (250 mmol/d); throughout the last 3, potassium was supplemented (as potassium bicarbonate) to either mid- or high-normal levels, 70 and 120 mmol/d. Salt sensitivity, defined as an increase in mean arterial blood pressure >/=3 mm Hg with salt loading, was deemed "moderate" if increasing

NaCl-induced renal vasoconstriction in salt-sensitive African Americans: antipressor and hemodynamic effects of potassium bicarbonate.

In 16 African Americans (blacks, 14 men, 2 women) with average admission mean arterial pressure (MAP, mm Hg) 99.9+/-3.5 (mean+/-SEM), we investigated whether NaCl-induced renal vasoconstriction attends salt sensitivity and, if so, whether supplemental KHCO3 ameliorates both conditions. Throughout a 3-week period under controlled metabolic conditions, all subjects ate diets containing 15 mmol NaCl and 30 mmol potassium (K+) (per 70 kg body wt [BW] per day). Throughout weeks 2 and 3, NaCl was loaded to 250 mmol/d; throughout week 3, dietary K+ was supplemented to 170 mmol/d (KHCO3). On the last day of each study week, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) using renal clearances of PAH and inulin. Ten subjects were salt sensitive (SS) (DeltaMAP >+5%) and 6 salt resistant (SR). In NaCl-loaded SS but not SR subjects, RBF (mL/min/1.73 m2) decreased from 920+/-75 to 828+/-46 (P<0.05); filtration fraction (FF, %) increased from 19. 4+/- to 21.4 (P<0.001); and renal vascular resistance (RVR) (10(3)xmm Hg/[mL/min]) increased from 101+/-8 to 131+/-10 (P<0.001). In all subjects combined, DeltaMAP varied inversely with DeltaRBF (r =-0.57, P=0.02) and directly with DeltaRVR (r = 0.65, P=0.006) and DeltaFF (r = 0.59, P=0.03), but not with MAP before NaCl loading. When supplemental KHCO3 abolished the pressor effect of NaCl in SS subjects, RBF was unaffected but GFR and FF decreased. The results show that in marginally K+-deficient blacks (1) NaCl-induced renal vasoconstrictive dysfunction attends salt sensitivity; (2) the dysfunction varies in extent directly with the NaCl-induced increase in blood pressure (BP); and (3) is complexly affected by supplemented KHCO3, GFR and FF decreasing but RBF not changing. In blacks, NaCl-induced renal vasoconstriction may be a pathogenetic event in salt sensitivity.

Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein contents.

Normal adult humans eating Western diets have chronic, low-grade metabolic acidosis, the severity of which is determined in part by the net rate of endogenous noncarbonic acid production (NEAP), which varies with diet. To prevent or reverse age-related sequelae of such diet-dependent acidosis (eg, bone and muscle loss), methods are needed for estimating and regulating NEAP. Because NEAP is difficult to measure directly, we sought a simple method to estimate it from diet-composition data. We focused on protein and potassium contents because the production of sulfuric acid from protein metabolism and bicarbonate from dietary potassium salts of organic acids are the major variable components of NEAP. Using steady state renal net acid excretion (RNAE) as an index of NEAP in 141 normal subjects eating 20 different diets, we found by multiple linear regression analysis that RNAE [mEq/d x 10460 kJ diet (mEq/d 2500 kcal)] was predictable (R2 = 0.62) from protein [g/d x 10460 kJ diet (g/d 2500 kcal); positive regression coefficient, P < 0.001] and potassium [mEq/d x 10460 kJ diet (mEq/d x 2500 kcal): negative regression coefficient, P = 0.001] contents, which were not themselves correlated. Among diets, 71% of the variation in RNAE could be accounted for by the ratio of protein (Pro) to potassium (K) content: RNAE = 62Pro/K - 17.9 (r = 0.84, R2 = 0.71, P < 0.001). Thus, by considering both the acidifying effect of protein and the alkalinizing effect of potassium (organic anions), NEAP can be predicted with confidence from the readily available contents of only 2 nutrients in foods. Provisionally, these findings allow estimation and regulation of NEAP through diet modification.