Geriatric Motorcycle-Related Outcomes: A Pennsylvania Multicenter Study.

INTRODUCTION: Geriatric patients (GeP) often experience increased morbidity and mortality following traumatic insult and as a result, require more specialized care due to lower physiologic reserve and underlying medical comorbidities. Motorcycle injuries (MCCI) occur across all age groups; however, no large-scale studies evaluating outcomes of GeP exist for this particular subset of patients. Data thus far are limited to elderly participation in recreational activities such as water and alpine skiing, snowboarding, equestrian, snowmobiles, bicycles, and all-terrain vehicles. We hypothesized that GeP with MCCI will have a higher rate of mortality when compared with their younger counterparts despite increased helmet usage. METHODS: We performed a multicenter retrospective review of MCCI patients at three Pennsylvania level I trauma centers from January 2016 to December 2020. Data were extracted from each institution's electronic medical records and trauma registry. GeP were defined as patients aged more than or equal to 65 y. The primary outcome was mortality. Secondary outcomes included ventilator days; hospital, intensive care unit, and intermediate unit length of stays; complications; and helmet use. 3:1 nongeriatric patients (NGeP) to GeP propensity score matching (PSM) was based on sex, abbreviated injury scale (AIS), and injury severity score (ISS). P ≤ 0.05 was considered significant. RESULTS: One thousand five hundred thirty eight patients were included (GeP: 7% [n = 113]; NGP: 93% [n = 1425]). Prior to PSM, GeP had higher median Charlson Comorbidity Index (GeP: 3.0 versus NGeP: 0.0; P ≤ 0.001) and greater helmet usage (GeP: 73.5% versus NGeP: 54.6%; P = 0.001). There was a statistically significant difference between age cohorts in terms of ISS (GeP: 10.0 versus NGeP: 6.0, P = 0.43). There was no significant difference for any AIS body region. Mortality rates were similar between groups (GeP: 1.7% versus NGeP: 2.6%; P = 0.99). After PSM matching for sex, AIS, and ISS, GeP had significantly more comorbidities than NGeP (P ≤ 0.05). There was no difference in trauma bay interventions or complications between cohorts. Mortality rates were similar (GeP: 1.8% versus NGeP: 3.2%; P = 0.417). Differences in ventilator days as well as intensive care unit length of stay, intermediate unit length of stay, and hospital length of stay were negligible. Helmet usage between groups were similar (GeP: 64.5% versus NGeP: 66.8%; P = 0.649). CONCLUSIONS: After matching for sex, ISS, and AIS, age more than 65 y was not associated with increased mortality following MCCI. There was also no significant difference in helmet use between groups. Further studies are needed to investigate the effects of other potential risk factors in the aging patient, such as frailty and anticoagulation use, before any recommendations regarding management of motorcycle-related injuries in GeP can be made.

A Novel PAK1-Notch1 Axis Regulates Crypt Homeostasis in Intestinal Inflammation.

BACKGROUND & AIMS: p21-activated kinase-1 (PAK1) belongs to a family of serine-threonine kinases and contributes to cellular pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), and Wingless-related integration site(Wnt)/ß-catenin, all of which are involved in intestinal homeostasis. Overexpression of PAK1 is linked to inflammatory bowel disease as well as colitis-associated cancer (CAC), and similarly was observed in interleukin (IL)10 knockout (KO) mice, a model of colitis and CAC. Here, we tested the effects of PAK1 deletion on intestinal inflammation and carcinogenesis in IL10 KO mice. METHODS: IL10/PAK1 double-knockout (DKO) mice were generated and development of colitis and CAC was analyzed. Large intestines were measured and prepared for histology or RNA isolation. Swiss rolls were stained with H&E and periodic acid-Schiff. Co-immunoprecipitation and immunofluorescence were performed using intestinal organoids, SW480, and normal human colon epithelial cells 1CT. RESULTS: When compared with IL10 KO mice, DKOs showed longer colons and prolonged crypts, despite having higher inflammation and numbers of dysplasia. Crypt hyperproliferation was associated with Notch1 activation and diminished crypt differentiation, indicated by a reduction of goblet cells. Gene expression analysis indicated up-regulation of the Notch1 target hairy and enhancer of split-1 and the stem cell receptor leucin-rich repeat-containing G-protein-coupled receptor 5 in DKO mice. Interestingly, the stem cell marker olfactomedin-4 was present in colonic tissue. Increased ß-catenin messenger RNA and cytoplasmic accumulation indicated aberrant Wnt signaling. Co-localization and direct interaction of Notch1 and PAK1 was found in colon epithelial cells. Notch1 activation abrogated this effect whereas silencing of PAK1 led to Notch1 activation. CONCLUSIONS: PAK1 contributes to the regulation of crypt homeostasis under inflammatory conditions by controlling Notch1. This identifies a novel PAK1-Notch1 axis in intestinal pathophysiology of inflammatory bowel disease and CAC.

Electrolyte Analysis and Replacement: Challenging a Paradigm in Surgical Patients.

Postoperative patients are susceptible to alterations in electrolyte homeostasis. Although electrolytes are replaced in critically ill patients, stable asymptomatic non-intensive care unit (ICU) patients often receive treatment of abnormal electrolytes. We hypothesize there is no proven benefit in asymptomatic patients. In 2016, using the electronic medical records and pharmacy database at a university academic medical center, we conducted a retrospective cost analysis of the frequency and cost of electrolyte analysis (basic metabolic panel [BMP], ionized calcium [Ca], magnesium [Mg], and phosphorus [P]) and replacement (potassium chloride [KCl], Mg, oral/iv Ca, oral/iv P) in perioperative patients. Patients without an oral diet order, with creatinine more than 1.4, age less than 16 years, admitted to the ICU, or with length of stay of more than 1 week were excluded. Nursing costs were calculated as a fraction of hourly wages per laboratory order or electrolyte replacement. One hundred thirteen patients met our criteria over 11 months. Mean length of stay was 4 days; mean age was 54 years; and creatinine was 0.67 ± 0.3. Electrolyte analysis laboratory orders (n = 1,045) totaled $6,978, and BMP was most frequently ordered accounting for 36% of laboratory costs. In total, 683 doses of electrolytes cost the pharmacy $1,780. Magnesium was most frequently replaced, followed by KCl, P, and Ca. Nursing cost associated with electrolyte analysis/replacement was $7,782. There is little evidence to support electrolyte analysis and replacement in stable asymptomatic noncritically ill patients, but their prevalence and cost ($146/case) in this study were substantial. Basic metabolic panels, pharmacy charges for potassium, and nursing staff costs accounted for the most significant portion of the total cost. Considering these data, further research should determine whether these practices are warranted.

p-21 Activated Kinase as a Molecular Target for Chemoprevention in Diabetes.

HYPOTHESIS: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling. Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here, we performed a mini-meta-analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways, to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using the online STRING database. Correlation studies were performed via systematic literature review to understand the effect of anti-diabetic drugs on PAK signaling. A mini-meta-analysis correlated multiple clinical studies and revealed the overall clinical response rate and percentage of adverse events in piogliazone (n = 53) and metformin (n = 91) treated patients with PAK-associated diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance), which were highly associated with Wnt, and G-protein signaling. The anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall, clinical response upon pioglitazone treatment was 53%. Seventy-nine percent of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM likely involves Wnt and G-protein signaling, which may be altered by the anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone may be promising in chemoprevention. However long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis.

HuR is an RNA-binding protein implicated in immune homeostasis and various cancers, including colorectal cancer. HuR binding to AU-rich elements within the 3' untranslated region of mRNAs encoding oncogenes, growth factors, and various cytokines leads message stability and translation. In this study, we evaluated HuR as a small-molecule target for preventing colorectal cancer in high-risk groups such as those with familial adenomatosis polyposis (FAP) or inflammatory bowel disease (IBD). In human specimens, levels of cytoplasmic HuR were increased in colonic epithelial cells from patients with IBD, IBD-cancer, FAP-adenoma, and colorectal cancer, but not in patients with IBD-dysplasia. Intraperitoneal injection of the HuR small-molecule inhibitor MS-444 in AOM/DSS mice, a model of IBD and inflammatory colon cancer, augmented DSS-induced weight loss and increased tumor multiplicity, size, and invasiveness. MS-444 treatment also abrogated tumor cell apoptosis and depleted tumor-associated eosinophils, accompanied by a decrease in IL18 and eotaxin-1. In contrast, HuR inhibition in APCMin mice, a model of FAP and colon cancer, diminished the number of small intestinal tumors generated. In this setting, fecal microbiota, evaluated by 16S rRNA gene amplicon sequencing, shifted to a state of reduced bacterial diversity, with an increased representation of Prevotella, Akkermansia, and Lachnospiraceae Taken together, our results indicate that HuR activation is an early event in FAP-adenoma but is not present in IBD-dysplasia. Furthermore, our results offer a preclinical proof of concept for HuR inhibition as an effective means of FAP chemoprevention, with caution advised in the setting of IBD. Cancer Res; 77(9); 2424-38. ©2017 AACR.

PAK1 promotes intestinal tumor initiation.

p21-activated kinase 1 (PAK1) is a serine/threonine kinase that is overexpressed in colorectal cancer. PAK1 is a target of mesalamine [5-aminosylicylic acid (5-ASA)], a common drug for the treatment of ulcerative colitis with prospective chemopreventive properties. Here, we investigated whether PAK1 deletion impedes tumorigenesis in murine intestinal cancer models. Ten-week-old APC(min) or APC(min)/PAK1(-/-) mice were monitored for 8 weeks, euthanized, and assessed for tumor number and size. Six- to 8-week-old PAK1(-/-) and wild-type (WT) mice received one 10 mg/kg intraperitoneal injection of azoxymethane (AOM) and four cycles of 1.7% dextran sodium sulfate (DSS) for 4 days followed by 14 days of regular water. Mice also received 5-ASA via diet. Tumor incidence and size was assessed via colonoscopy and pathology. Molecular targets of PAK1 and 5-ASA were evaluated via immunohistochemistry (IHC) in both models. PAK1 deletion reduced tumor multiplicity and tumor burden but did not alter average tumor size in APC(min) mice. IHC revealed that PAK1 deletion reduced p-AKT, ß-catenin, and c-Myc expression in APC(min) adenomas. Colonoscopy and pathologic analysis revealed that PAK1 deletion reduced tumor multiplicity without affecting tumor size in AOM/DSS-treated mice. 5-ASA treatment and PAK1 deletion impeded tumor multiplicity and dysplastic lesions in AOM/DSS mice. IHC further revealed that 5-ASA blocked ß-catenin signaling via inhibition of PAK1/p-AKT. These data indicate that PAK1 contributes to initiation of intestinal carcinogenesis.

PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation.

P21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases with both kinase and scaffolding activity. Here, we investigated the effects of inflammation on PAK1 signaling and its role in colitis-driven carcinogenesis. PAK1 and p-PAK1 (Thr423) were assessed by immunohistochemistry, immunofluorescence, and Western blot. C57BL6/J wildtype mice were treated with a single intraperitoneal TNFα injection. Small intestinal organoids from these mice and from PAK1-KO mice were cultured with TNFα. NF-κB and PPARγ were analyzed upon PAK1 overexpression and silencing for transcriptional/translational regulation. PAK1 expression and activation was increased on the luminal intestinal epithelial surface in inflammatory bowel disease and colitis-associated cancer. PAK1 was phosphorylated upon treatment with IFNγ, IL-1ß, and TNFα. In vivo, mice administered with TNFα showed increased p-PAK1 in intestinal villi, which was associated with nuclear p65 and NF-κB activation. p65 nuclear translocation downstream of TNFα was strongly inhibited in PAK1-KO small intestinal organoids. PAK1 overexpression induced a PAK1-p65 interaction as visualized by co-immunoprecipitation, nuclear translocation, and increased NF-κB transactivation, all of which were impeded by kinase-dead PAK1. Moreover, PAK1 overexpression downregulated PPARγ and mesalamine recovered PPARγ through PAK1 inhibition. On the other hand PAK1 silencing inhibited NF-κB, which was recovered using BADGE, a PPARγ antagonist. Altogether these data demonstrate that PAK1 overexpression and activation in inflammation and colitis-associated cancer promote NF-κB activity via suppression of PPARγ in intestinal epithelial cells.

Overexpression of PAK1 promotes cell survival in inflammatory bowel diseases and colitis-associated cancer.

BACKGROUND: Chronic gut inflammation predisposes to the development of colorectal cancer and increased mortality. Use of mesalamine (5-ASA) in the treatment of ulcerative colitis modulates the risk of neoplastic progression. p21 activated kinase 1 (PAK1) mediates 5-ASA activity by orchestrating MAPK signaling, Wnt-ß catenin pathway, and cell adhesion; all implicated in the colon carcinogenesis. We evaluated the role of PAK1 in IBD and in colitis-associated cancer (CAC). METHODS AND RESULTS: PAK1 expression was scored by immunohistochemistry in human samples from IBD, CAC, and in normal mucosa. Compared with controls, a higher PAK1 expression was detected in IBD which further increased in CAC. The consequence of PAK1 overexpression was investigated using normal diploid colon epithelial cells (HCEC-1CT), which showed higher proliferation and decreased apoptosis on overexpression of PAK1. Analysis of IBD and CAC samples showed activation of AKT (p-AKT). However, mTOR pathway was activated in IBD but not in CAC. Treatment of cells with specific inhibitors (PD98059/LY294002/rapamycin) of growth signaling pathways (MEK/PI3K/mTOR) demonstrated that in HCEC-1CT, PAK1 expression is regulated by MEK, PI3K, and mTOR. In colorectal cancer cell lines, PAK1, and beta-catenin expression correlated and inhibition of PAK1 and addition of 5-ASA elicited similar molecular affects by reducing ERK and AKT activation. Moreover, 5-ASA disrupted PAK1 interaction and colocalization with ß-catenin. CONCLUSIONS: Our data indicate that (1) PAK1 is upregulated in IBD and CAC (2) PAK1 overexpression is associated with activation of PI3K-AKT/mTOR prosurvival pathways in IBD.

Republished: tracing PAKs from GI inflammation to cancer.

P-21 activated kinases (PAKs) are effectors of Rac1/Cdc42 which coordinate signals from the cell membrane to the nucleus. Activation of PAKs drive important signalling pathways including mitogen activated protein kinase, phospoinositide 3-kinase (PI3K/AKT), NF-κB and Wnt/ß-catenin. Intestinal PAK1 expression increases with inflammation and malignant transformation, although the biological relevance of PAKs in the development and progression of GI disease is only incompletely understood. This review highlights the importance of altered PAK activation within GI inflammation, emphasises its effect on oncogenic signalling and discusses PAKs as therapeutic targets of chemoprevention.

Tracing PAKs from GI inflammation to cancer.

P-21 activated kinases (PAKs) are effectors of Rac1/Cdc42 which coordinate signals from the cell membrane to the nucleus. Activation of PAKs drive important signalling pathways including mitogen activated protein kinase, phospoinositide 3-kinase (PI3K/AKT), NF-κB and Wnt/ß-catenin. Intestinal PAK1 expression increases with inflammation and malignant transformation, although the biological relevance of PAKs in the development and progression of GI disease is only incompletely understood. This review highlights the importance of altered PAK activation within GI inflammation, emphasises its effect on oncogenic signalling and discusses PAKs as therapeutic targets of chemoprevention.

Modulation of N-glycosylation by mesalamine facilitates membranous E-cadherin expression in colon epithelial cells.

Genome wide association studies have implicated intestinal barrier function genes in the pathogenesis of ulcerative colitis. One of such loci CDH1, encoding E-cadherin, a transmembrane glycoprotein with known tumor suppressor functions, is also linked to the susceptibility to colorectal cancer. Loss of membranous E-cadherin expression is common in both colitis and cancer. We have recently demonstrated that mesalamine (5-ASA); the anti-inflammatory drug used to treat ulcerative colitis, induces membranous expression of E-cadherin and increases intercellular adhesion. Using colorectal cancer epithelial cells with aberrant E-cadherin expression, we investigated the mechanism underlying such an effect of 5-ASA. Post-translational modification of E-cadherin glycosylation was analyzed by biotin/streptavidin detection of sialylated glycoproteins. GnT-III (N-acetylglucosaminyltransferase III) expression was assessed by qRT-PCR, Western blot and immunofluorescence. GnT-III activity was analyzed by reactivity with E-4/L-4-PHA. Expression, localization and interaction of E-cadherin and ß-catenin were analyzed by Western blot, immunocytochemistry and RNA interference. 5-ASA activity modulated E-cadherin glycosylation and increased both mRNA and protein levels of GnT-III and its activity as detected by increased E4-lectin reactivity. Intestinal APC(Min) polyps in mice showed low expression of GnT-III and 5-ASA was effective in increasing its expression. The data demonstrated that remodeling of glycans by GnT-III mediated bisect glycosylation, contributes to the membranous retention of E-cadherin by 5-ASA; facilitating intercellular adhesion. Induction of membranous expression of E-cadherin by 5-ASA is a novel mechanism for mucosal healing in colitis that might impede tumor progression by modulation of GnT-III expression.

Thymoquinone attenuates tumor growth in ApcMin mice by interference with Wnt-signaling.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) are at increased risk for the development of colorectal cancer. Surgery and chemoprevention are the most effective means to prevent cancer development. Thymoquinone (TQ) is considered the main compound of the volatile Nigella sativa seed oil and has been reported to possess anticarcinogenic properties. In this study we evaluated the chemopreventive properties of TQ in a mouse model of FAP. METHODS: APCMin mice were fed with chow containing 37.5 mg/kg or 375 mg/kg TQ for 12 weeks. H&E stained intestine tissue sections were assessed for tumor number, localization, size, and grade. Immunohistochemistry for ß-catenin, c-myc, Ki-67 and TUNEL-staining was performed to investigate TQ's effect on major colorectal cancer pathways. TQ's impact on GSK-3ß and ß-catenin were studied in RKO cells. RESULTS: 375 mg/kg but not 37.5 mg/kg TQ decreased the number of large polyps in the small intestine of APCMin mice. TQ induced apoptosis in the neoplastic tissue but not in the normal mucosa. Furthermore, upon TQ treatment, ß-catenin was retained at the membrane and c-myc decreased in the nucleus, which was associated with a reduced cell proliferation in the villi. In vitro, TQ activated GSK-3ß, which induced membranous localization of ß-catenin and reduced nuclear c-myc expression. CONCLUSIONS: In summary, TQ interferes with polyp progression in ApcMin mice through induction of tumor-cell specific apoptosis and by modulating Wnt signaling through activation of GSK-3ß. Nigella sativa oil (or TQ) might be useful as nutritional supplement to complement surgery and chemoprevention in FAP.

Mesalamine modulates intercellular adhesion through inhibition of p-21 activated kinase-1.

Mesalamine (5-ASA) is widely used for the treatment of ulcerative colitis, a remitting condition characterized by chronic inflammation of the colon. Knowledge about the molecular and cellular targets of 5-ASA is limited and a clear understanding of its activity in intestinal homeostasis and interference with neoplastic progression is lacking. We sought to identify molecular pathways interfered by 5-ASA, using CRC cell lines with different genetic background. Microarray was performed for gene expression profile of 5-ASA-treated and untreated cells (HCT116 and HT29). Filtering and analysis of data identified three oncogenic pathways interfered by 5-ASA: MAPK/ERK pathway, cell adhesion and ß-catenin/Wnt signaling. PAK1 emerged as a consensus target of 5-ASA, orchestrating these pathways. We further investigated the effect of 5-ASA on cell adhesion. 5-ASA increased cell adhesion which was measured by cell adhesion assay and transcellular-resistance measurement. Moreover, 5-ASA treatment restored membranous expression of adhesion molecules E-cadherin and ß-catenin. Role of PAK1 as a mediator of mesalamine activity was validated in vitro and in vivo. Inhibition of PAK1 by RNA interference also increased cell adhesion. PAK1 expression was elevated in APC(min) polyps and 5-ASA treatment reduced its expression. Our data demonstrates novel pharmacological mechanism of mesalamine in modulation of cell adhesion and role of PAK1 in APC(min) polyposis. We propose that inhibition of PAK1 expression by 5-ASA can impede with neoplastic progression in colorectal carcinogenesis. The mechanism of PAK1 inhibition and induction of membranous translocation of adhesion proteins by 5-ASA might be independent of its known anti-inflammatory action.

MSH3-deficiency initiates EMAST without oncogenic transformation of human colon epithelial cells.

BACKGROUND/AIM: Elevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature in certain cases of sporadic colorectal cancer and has been linked to MSH3-deficiency. It is currently controversial whether EMAST is associated with oncogenic properties in humans, specifically as cancer development in Msh3-deficient mice is not enhanced. However, a mutator phenotype is different between species as the genetic positions of repetitive sequences are not conserved. Here we studied the molecular effects of human MSH3-deficiency. METHODS: HCT116 and HCT116+chr3 (both MSH3-deficient) and primary human colon epithelial cells (HCEC, MSH3-wildtype) were stably transfected with an EGFP-based reporter plasmid for the detection of frameshift mutations within an [AAAG]17 repeat. MSH3 was silenced by shRNA and changes in protein expression were analyzed by shotgun proteomics. Colony forming assay was used to determine oncogenic transformation and double strand breaks (DSBs) were assessed by Comet assay. RESULTS: Despite differential MLH1 expression, both HCT116 and HCT116+chr3 cells displayed comparable high mutation rates (about 4×10(-4)) at [AAAG]17 repeats. Silencing of MSH3 in HCECs leads to a remarkable increased frameshift mutations in [AAAG]17 repeats whereas [CA]13 repeats were less affected. Upon MSH3-silencing, significant changes in the expression of 202 proteins were detected. Pathway analysis revealed overexpression of proteins involved in double strand break repair (MRE11 and RAD50), apoptosis, L1 recycling, and repression of proteins involved in metabolism, tRNA aminoacylation, and gene expression. MSH3-silencing did not induce oncogenic transformation and DSBs increased 2-fold. CONCLUSIONS: MSH3-deficiency in human colon epithelial cells results in EMAST, formation of DSBs and significant changes of the proteome but lacks oncogenic transformation. Thus, MSH3-deficiency alone is unlikely to drive human colon carcinogenesis.

Effect of inclining strain on the crystal lattice along an extended series of lanthanide hydroxysulfates Ln(OH)SO4 (Ln = Pr-Yb, except Pm).

A series of trivalent lanthanide hydroxysulfates, Ln(OH)SO(4), (Ln = Pr through Yb, except radioactive Pm) has been synthesized via hydrothermal methods from Ln(2)(SO(4))(3)·8H(2)O by reaction with aqueous NaOH at 170 °C in Teflon lined Parr steel autoclaves, and were characterized by single crystal X-ray diffraction and FT-IR spectroscopy. Two types of arrangements were found in the solid state. The lighter (Ln = Pr-Nd, Sm-Gd) and heavier lanthanide(III) hydroxysulfates (Tb-Yb) are each isostructural. Both structure types exhibit the monoclinic space group P2(1)/n, but the unit cell content is doubled with two crystallographically distinct LnO(8) polyhedra for the heavier lanthanide compounds. The lighter complexes maintain the coordination number 9, forming a three-dimensional extended lattice. The heavier counterparts exhibit the coordination number 8, and arrange as infinite columns of two crystallographically different LnO(8) polyhedra, while extending along the "c" axis. These columns of LnO(8) polyhedra are surrounded and separated by six columns of sulfate ions, also elongating in the "c" direction. The rigid sulfate entities seem to obstruct the closing in of the lighter LnO(9) polyhedra, and show an inclining degree of torsion into the "ac" layers. The crystal lattice of the lighter 4f complexes can sufficiently withstand the tension buildup, caused by the decreasing Ln(3+) radius, up to Gd(OH)SO(4). The energy profile of this structural arrangement then seems to exceed levels at which this structure type is favorable. The lattice arrangement of the heavier Ln-analogues seems to offer a lower energy profile. This appears to be the preferred arrangement for the heavier lanthanide hydroxysulfates, whose crystal lattice exhibits more flexibility, as the coordination sphere of these analogues is less crowded. The IR absorbance frequencies of the hydroxide ligands correlate as a function of the Ln(3+) ionic radius. This corresponds well with the X-ray single crystal analysis data.